1
40
61
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1002/ardp.201500293" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/ardp.201500293</a>
Pages
252–267
Issue
4
Volume
349
Dublin Core
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Title
A name given to the resource
Synthesis and Biological Evaluation of Pentacycloundecylamines and Triquinylamines as Voltage-Gated Calcium Channel Blockers.
Publisher
An entity responsible for making the resource available
Archiv der Pharmazie
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-04
Subject
The topic of the resource
Alicyclic/chemical synthesis/*chemistry/pharmacology; Amines/chemical synthesis/*chemistry/pharmacology; Animals; Apoptosis/drug effects; Calcium Channel Blockers/chemical synthesis/*chemistry/pharmacology; Calcium Channels; Calcium/*metabolism; Cell Survival/drug effects; Hydrocarbons; Hydrogen Peroxide/pharmacology; L-Lactate Dehydrogenase/metabolism; L-type calcium channel (LTCC) blockers; L-Type/*metabolism; Multifunctional drugs; Neurodegeneration; PC12 Cells; Pentacycloundecylamine; Quinones/chemical synthesis/*chemistry/pharmacology; Rats; Structure-Activity Relationship; Triquinylamine
Creator
An entity primarily responsible for making the resource
Young Lois-May; Geldenhuys Werner J; Domingo Olwen C; Malan Sarel F; Van der Schyf Cornelis J
Description
An account of the resource
Preclinical studies for neurodegenerative diseases have shown a multi-targeted approach to be successful in the treatment of these complex disorders with several pathoetiological pathways. Polycyclic compounds, such as NGP1-01 (7a), have demonstrated the ability to target multiple mechanisms of the complex etiology and are referred to as multifunctional compounds. These compounds have served as scaffolds with the ability to attenuate Ca(2+) overload and excitotoxicity through several pathways. In this study, our focus was on mitigating Ca(2+) overload through the L-type calcium channels (LTCC). Here, we report the synthesis and biological evaluation of several novel polycyclic compounds. We determined the IC50 values for both the pentacycloundecylamines and the triquinylamines by means of a high-throughput fluorescence calcium flux assay utilizing Fura-2/AM. The potential of these compounds to offer protection against hydrogen peroxide-induced cell death was also evaluated. Overall,
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1002/ardp.201500293" target="_blank" rel="noreferrer noopener">10.1002/ardp.201500293</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2016
Alicyclic/chemical synthesis/*chemistry/pharmacology
Amines/chemical synthesis/*chemistry/pharmacology
Animals
Apoptosis/drug effects
Archiv der Pharmazie
Calcium Channel Blockers/chemical synthesis/*chemistry/pharmacology
Calcium Channels
Calcium/*metabolism
Cell Survival/drug effects
Domingo Olwen C
Geldenhuys Werner J
Hydrocarbons
Hydrogen Peroxide/pharmacology
L-Lactate Dehydrogenase/metabolism
L-type calcium channel (LTCC) blockers
L-Type/*metabolism
Malan Sarel F
Multifunctional drugs
Neurodegeneration
PC12 Cells
Pentacycloundecylamine
Quinones/chemical synthesis/*chemistry/pharmacology
Rats
Structure-Activity Relationship
Triquinylamine
Van der Schyf Cornelis J
Young Lois-May
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1002/cbic.201300770" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/cbic.201300770</a>
Pages
1591–1598
Issue
11
Volume
15
Dublin Core
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Title
A name given to the resource
Methyl Yellow: A Potential Drug Scaffold for Parkinson's Disease.
Publisher
An entity responsible for making the resource available
Chembiochem : a European journal of chemical biology
Date
A point or period of time associated with an event in the lifecycle of the resource
2014
2014-07
Subject
The topic of the resource
*MAO-B inhibitor; *methyl yellow; *MPTP mouse model; *Parkinson's disease; *TMRM
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Kochi Akiko; Lin Li; Sutariya Vijaykumar; Dluzen Dean E; Van der Schyf Cornelis J; Lim Mi Hee
Description
An account of the resource
Parkinson's disease (PD) is an age-related neurodegenerative disease affecting movement. To date, there are no currently available therapeutic agents which can prevent or slow disease progression. Here, we evaluated an azobenzene derivative, methyl yellow (MY), as a potential drug scaffold for PD; its inhibitory activity toward monoamine oxidase B (MAO-B) as well as drug-like properties were investigated. The inhibitory effect of MY on MAO activity was determined by a MAO enzyme inhibition assay. In addition, the in vitro properties of MY as a drug candidate (e.g., blood-brain barrier (BBB) permeability, serum albumin binding, drug efflux through P-glycoprotein (P-gp), drug metabolism by P450, and mitochondrial toxicity) were examined. In vivo effectiveness of MY was also evaluated in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonian mouse model. MY selectively inhibited MAO-B in a dose-dependent and reversible manner. MY was BBB-permeable, bound relatively weakly to serum albumin, was an unlikely substrate for both systems of P-gp and P450, and did not cause mitochondrial toxicity. Results from the MPTP Parkinsonian mouse model indicated that, upon treatment with MY, neurotoxicity induced by MPTP was mitigated. Investigations of MY demonstrate its inhibitory activity toward MAO-B, compliant properties for drug consideration, and its neuroprotective capability in the MPTP Parkinsonian mouse model. These data provide insights into potential use, optimization, and new design of azobenzene derivatives for PD treatment.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1002/cbic.201300770" target="_blank" rel="noreferrer noopener">10.1002/cbic.201300770</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*MAO-B inhibitor
*methyl yellow
*MPTP mouse model
*Parkinson's disease
*TMRM
2014
Chembiochem : a European journal of chemical biology
Dluzen Dean E
Geldenhuys Werner J
Kochi Akiko
Lim Mi Hee
Lin Li
Sutariya Vijaykumar
Van der Schyf Cornelis J
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1002/jcp.22704" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/jcp.22704</a>
Pages
70–76
Issue
1
Volume
227
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Primary cilia regulates the directional migration and barrier integrity of endothelial cells through the modulation of hsp27 dependent actin cytoskeletal organization.
Publisher
An entity responsible for making the resource available
Journal of cellular physiology
Date
A point or period of time associated with an event in the lifecycle of the resource
2012
2012-01
Subject
The topic of the resource
*Cell Movement; Actin Cytoskeleton/*metabolism; Animals; Blotting; Capillary Permeability/*physiology; Cell Adhesion; Cilia/metabolism; Endothelial Cells/cytology/*metabolism; Fluorescent Antibody Technique; Focal Adhesions/metabolism; HSP27 Heat-Shock Proteins/*metabolism; Mice; Polycystic Kidney Diseases/physiopathology; Signal Transduction/physiology; Transgenic; Western
Creator
An entity primarily responsible for making the resource
Jones Thomas J; Adapala Ravi K; Geldenhuys Werner J; Bursley Chris; AbouAlaiwi Wissam A; Nauli Surya M; Thodeti Charles K
Description
An account of the resource
Cilia are mechanosensing organelles that communicate extracellular signals into intracellular responses. Altered functions of primary cilia play a key role in the development of various diseases including polycystic kidney disease. Here, we show that endothelial cells from the oak ridge polycystic kidney (Tg737(orpk/orpk) ) mouse, with impaired cilia assembly, exhibit a reduction in the actin stress fibers and focal adhesions compared to wild-type (WT). In contrast, endothelial cells from polycystin-1 deficient mice (pkd1(null/null) ), with impaired cilia function, display robust stress fibers, and focal adhesion assembly. We found that the Tg737(orpk/orpk) cells exhibit impaired directional migration and endothelial cell monolayer permeability compared to the WT and pkd1(null/null) cells. Finally, we found that the expression of heat shock protein 27 (hsp27) and the phosphorylation of focal adhesion kinase (FAK) are downregulated in the Tg737(orpk/orpk) cells and overexpression of hsp27 restored both FAK phosphorylation and cell migration. Taken together, these results demonstrate that disruption of the primary cilia structure or function compromises the endothelium through the suppression of hsp27 dependent actin organization and focal adhesion formation, which may contribute to the vascular dysfunction in ciliopathies.
Identifier
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<a href="http://doi.org/10.1002/jcp.22704" target="_blank" rel="noreferrer noopener">10.1002/jcp.22704</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Cell Movement
2012
AbouAlaiwi Wissam A
Actin Cytoskeleton/*metabolism
Adapala Ravi K
Animals
Blotting
Bursley Chris
Capillary Permeability/*physiology
Cell Adhesion
Cilia/metabolism
Department of Integrative Medical Sciences
Endothelial Cells/cytology/*metabolism
Fluorescent Antibody Technique
Focal Adhesions/metabolism
Geldenhuys Werner J
HSP27 Heat-Shock Proteins/*metabolism
Jones Thomas J
Journal of cellular physiology
Mice
Nauli Surya M
NEOMED College of Medicine
Polycystic Kidney Diseases/physiopathology
Signal Transduction/physiology
Thodeti Charles K
Transgenic
Western
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1007/s00395-015-0471-z" target="_blank" rel="noreferrer noopener">http://doi.org/10.1007/s00395-015-0471-z</a>
Pages
19–19
Issue
2
Volume
110
Dublin Core
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Title
A name given to the resource
Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress.
Publisher
An entity responsible for making the resource available
Basic research in cardiology
Date
A point or period of time associated with an event in the lifecycle of the resource
2015
2015-03
Subject
The topic of the resource
Animals; Cardiac/cytology/*drug effects; Cell Differentiation/drug effects; Flow Cytometry; Knockout; Male; Mice; Mitochondrial Membranes/metabolism; Mitochondrial Proteins/metabolism; Myocytes; Oxidative Stress/drug effects/*physiology; Rats; Real-Time Polymerase Chain Reaction; Stem Cells/cytology/*drug effects; Thiazolidinediones/*pharmacology; Zucker
Creator
An entity primarily responsible for making the resource
Logan Suzanna J; Yin Liya; Geldenhuys Werner J; Enrick Molly K; Stevanov Kelly M; Carroll Richard T; Ohanyan Vahagn A; Kolz Christopher L; Chilian William M
Description
An account of the resource
Ischemic heart disease (IHD) is a leading cause of death worldwide, and regenerative therapies through exogenous stem cell delivery hold promising potential. One limitation of such therapies is the vulnerability of stem cells to the oxidative environment associated with IHD. Accordingly, manipulation of stem cell mitochondrial metabolism may be an effective strategy to improve survival of stem cells under oxidative stress. MitoNEET is a redox-sensitive, mitochondrial target of thiazolidinediones (TZDs), and influences cellular oxidative capacity. Pharmacological targeting of mitoNEET with the novel TZD, mitoNEET Ligand-1 (NL-1), improved cardiac stem cell (CSC) survival compared to vehicle (0.1% DMSO) during in vitro oxidative stress (H2O2). 10 muM NL-1 also reduced CSC maximal oxygen consumption rate (OCR) compared to vehicle. Following treatment with dexamethasone, CSC maximal OCR increased compared to baseline, but NL-1 prevented this effect. Smooth muscle alpha-actin expression increased significantly in CSC following differentiation compared to baseline, irrespective of NL-1 treatment. When CSCs were treated with glucose oxidase for 7 days, NL-1 significantly improved cell survival compared to vehicle (trypan blue exclusion). NL-1 treatment of cells isolated from mitoNEET knockout mice did not increase CSC survival with H2O2 treatment. Following intramyocardial injection of CSCs into Zucker obese fatty rats, NL-1 significantly improved CSC survival after 24 h, but not after 10 days. These data suggest that pharmacological targeting of mitoNEET with TZDs may acutely protect stem cells following transplantation into an oxidative environment. Continued treatment or manipulation of mitochondrial metabolism may be necessary to produce long-term benefits related to stem cell therapies.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1007/s00395-015-0471-z" target="_blank" rel="noreferrer noopener">10.1007/s00395-015-0471-z</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2015
Animals
Basic research in cardiology
Cardiac/cytology/*drug effects
Carroll Richard T
Cell Differentiation/drug effects
Chilian William M
Department of Integrative Medical Sciences
Enrick Molly K
Flow Cytometry
Geldenhuys Werner J
Knockout
Kolz Christopher L
Logan Suzanna J
Male
Mice
Mitochondrial Membranes/metabolism
Mitochondrial Proteins/metabolism
Myocytes
NEOMED College of Medicine
Ohanyan Vahagn A
Oxidative Stress/drug effects/*physiology
Rats
Real-Time Polymerase Chain Reaction
Stem Cells/cytology/*drug effects
Stevanov Kelly M
Thiazolidinediones/*pharmacology
Yin Liya
Zucker
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1007/s13346-012-0117-8" target="_blank" rel="noreferrer noopener">http://doi.org/10.1007/s13346-012-0117-8</a>
Pages
309–317
Issue
4
Volume
3
Dublin Core
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Title
A name given to the resource
Engineering triiodothyronine (T3) nanoparticle for use in ischemic brain stroke.
Publisher
An entity responsible for making the resource available
Drug delivery and translational research
Date
A point or period of time associated with an event in the lifecycle of the resource
2013
2013-08
Subject
The topic of the resource
Blood-brain barrier; Brain stroke; Nanoparticles; Neuroprotection; Thyroid hormone
Creator
An entity primarily responsible for making the resource
Mdzinarishvili Alexander; Sutariya Vijaykumar; Talasila Phani K; Geldenhuys Werner J; Sadana Prabodh
Description
An account of the resource
A potential means of pharmacological management of ischemic stroke is rapid intervention using potent neuroprotective agents. Thyroid hormone (T3) has been shown to protect against ischemic damage in middle cerebral artery occlusion (MCAO) model of ischemic brain stroke. While thyroid hormone is permeable across the blood-brain barrier, we hypothesized that efficacy of thyroid hormone in ischemic brain stroke can be enhanced by encapsulation in nanoparticulate delivery vehicles. We tested our hypothesis by generating poly-(lactide-co-glycolide)-polyethyleneglycol (PLGA-b-PEG) nanoparticles that are either coated with glutathione or are not coated. We have previously reported that glutathione coating of PLGA-PEG nanoparticles is an efficient means of brain targeted drug delivery. Encapsulation of T3 in PLGA-PEG delivery vehicle resulted in particles that were in the nano range and exhibited a zeta potential of -6.51 mV (uncoated) or -1.70 mV (coated). We observed that both glutathione-coated and uncoated nanoparticles are taken up in cells wherein they stimulated the expression of thyroid hormone response element driven reporter robustly. In MCAO model of ischemic stroke, significant benefit of administering T3 in nanoparticulate form was observed over injection of a T3 solution. A 34 % decrease in tissue infarction and a 59 % decrease in brain edema were seen upon administration of T3 solution in MCAO stroke model. Corresponding measurements for uncoated T3 nanoparticles were 51 % and 68 %, whereas for the glutathione coated were 58 % and 75 %. Our study demonstrates that using nanoparticle formulations can significantly improve the efficacy of neuroprotective drugs in ischemic brain stroke.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1007/s13346-012-0117-8" target="_blank" rel="noreferrer noopener">10.1007/s13346-012-0117-8</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2013
Blood-brain barrier
Brain stroke
Department of Pharmaceutical Sciences
Department of Pharmacy Practice
Drug delivery and translational research
Geldenhuys Werner J
Mdzinarishvili Alexander
Nanoparticles
NEOMED College of Graduate Studies
NEOMED College of Pharmacy
Neuroprotection
Sadana Prabodh
Sutariya Vijaykumar
Talasila Phani K
Thyroid hormone
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/B978-0-12-386467-3.00006-6" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/B978-0-12-386467-3.00006-6</a>
Pages
107–125
Volume
100
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Multimodal drugs and their future for Alzheimer's and Parkinson's disease.
Publisher
An entity responsible for making the resource available
International review of neurobiology
Date
A point or period of time associated with an event in the lifecycle of the resource
2011
1905-07
Subject
The topic of the resource
Alzheimer Disease/*drug therapy/*enzymology/prevention & control; Animals; Combined Modality Therapy/*methods; Forecasting; Humans; Monoamine Oxidase Inhibitors/*pharmacology/therapeutic use; Parkinson Disease/*drug therapy/*enzymology/prevention & control
Creator
An entity primarily responsible for making the resource
Van der Schyf Cornelis J; Geldenhuys Werner J
Description
An account of the resource
This chapter discusses the rationale for developing multimodal or multifunctional drugs (also called designed multiple ligands or DMLs) aimed at disease-modifying treatment strategies for the most common neurodegenerative diseases Alzheimer's and Parkinson's disease (AD and PD). Both the prevalence and incidence of AD and PD have seen consistent and dramatic increases, a disconcerting phenomenon which, ironically, has been attributed to extended life expectancy brought about by better health care globally. In spite of these statistics, the development and introduction to the clinic of new therapies proven to prevent or delay the onset of AD and PD have been disappointing. Evidence has accumulated to suggest that the etiopathology of these diseases is extremely complex, with an array of potential drug targets located within a number of deleterious biochemical pathways. Therefore, in these diseases, it is unlikely that the complex pathoetiological cascade leading to disease initiation or progression will be mitigated by any one drug acting on a single pathway or target. The pursuit of novel DMLs may offer far better outcomes. Although certainly not the only, and perhaps not even the best, approach but farthest along the drug development pipeline in the DML paradigm are drugs that combine inhibition of monoamine oxidase with associated etiological targets unique to either AD or PD. These compounds will constitute the major focus of this chapter, which will also explore radically new paradigms that seek to combine cognitive enhancers with proneurogenesis compounds.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/B978-0-12-386467-3.00006-6" target="_blank" rel="noreferrer noopener">10.1016/B978-0-12-386467-3.00006-6</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2011
Alzheimer Disease/*drug therapy/*enzymology/prevention & control
Animals
Combined Modality Therapy/*methods
Forecasting
Geldenhuys Werner J
Humans
International review of neurobiology
Monoamine Oxidase Inhibitors/*pharmacology/therapeutic use
Parkinson Disease/*drug therapy/*enzymology/prevention & control
Van der Schyf Cornelis J
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmc.2006.09.060" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmc.2006.09.060</a>
Pages
1525–1532
Issue
3
Volume
15
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Structure-activity relationships of pentacycloundecylamines at the
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry
Date
A point or period of time associated with an event in the lifecycle of the resource
2007
2007-02
Subject
The topic of the resource
Amines/chemical synthesis/chemistry/*pharmacology; Animals; Brain/drug effects; Dizocilpine Maleate/pharmacology; Excitatory Amino Acid Antagonists/*pharmacology; Inbred ICR; Ion Channels; Male; Mice; Models; Molecular; N-Methyl-D-Aspartate/*antagonists & inhibitors; Phencyclidine/analogs & derivatives; Piperidines/pharmacology; Radioligand Assay; Receptors; Structure-Activity Relationship; Synaptosomes/*drug effects; Thiophenes/pharmacology
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Malan Sarel F; Bloomquist Jeffrey R; Van der Schyf Cornelis J
Description
An account of the resource
Prompted by our interest in neuroprotective agents with multiple mechanisms of action, we assessed the structure-activity relationship of a series of pentacycloundecylamine derivatives previously shown to have both L-type calcium channel blocking activity and N-methyl-d-aspartate receptor (NMDAR) antagonistic activity. We utilized a functional assay to measure NMDAR channel block using (45)Ca(2+) influx into synaptoneurosomes. The cage amine
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmc.2006.09.060" target="_blank" rel="noreferrer noopener">10.1016/j.bmc.2006.09.060</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2007
Amines/chemical synthesis/chemistry/*pharmacology
Animals
Bioorganic & medicinal chemistry
Bloomquist Jeffrey R
Brain/drug effects
Dizocilpine Maleate/pharmacology
Excitatory Amino Acid Antagonists/*pharmacology
Geldenhuys Werner J
Inbred ICR
Ion Channels
Malan Sarel F
Male
Mice
Models
Molecular
N-Methyl-D-Aspartate/*antagonists & inhibitors
Phencyclidine/analogs & derivatives
Piperidines/pharmacology
Radioligand Assay
Receptors
Structure-Activity Relationship
Synaptosomes/*drug effects
Thiophenes/pharmacology
Van der Schyf Cornelis J
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2009.12.088" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2009.12.088</a>
Pages
819–823
Issue
3
Volume
20
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Structure-based design of a thiazolidinedione which targets the mitochondrial protein mitoNEET.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2010
2010-02
Subject
The topic of the resource
*Drug Design; Animals; Binding Sites/drug effects/physiology; Dose-Response Relationship; Drug; Drug Delivery Systems/*methods; Liver/drug effects/metabolism; Mitochondria; Mitochondrial Proteins/*metabolism; Protein Structure; Rats; Secondary; Structure-Activity Relationship; Thiazolidinediones/administration & dosage/*chemical synthesis/*metabolism
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Funk Max O; Barnes Kendra F; Carroll Richard T
Description
An account of the resource
Several PPAR-gamma agonists containing a thiazolidinedione moiety (referred to as glitazones) have been proposed to be neuroprotective and appear to alter mitochondrial function. Recently, a search for mitochondrial proteins that bind pioglitazone identified a novel protein, mitoNEET, which was later shown to regulate the oxidative capacity of the mitochondria. This identified an alternative target for the glitazones suggesting a possible new drug target for the treatment of neurodegenerative diseases. Molecular docking studies employing the reported crystal structure revealed five possible binding pockets on mitoNEET. We focused on two sites based on their physical characteristics. Using binding information gained from the analysis of two glitazones docked in these pockets, we designed and synthesized a ligand (NL-1) that would preferentially bind to site 1. Based on [(3)H]-binding data of the glitazones and comparisons to computer generated K(i)s, we were able to predict that site 1 was likely the target of the glitazones. NL-1 uncoupled isolated mitochondrial complex I respiration with an IC(50) of 2.4 microM and inhibited state III respiration up to 45%. To investigate the ability of NL-1 to block rotenone initiated free radicals from complex I, we found it was able to protect the human neuronal cell line SH-SY5Y against rotenone induced cell death. These data demonstrate that mitoNEET is a viable target for the design and synthesis of novel therapeutic agents aimed at altering mitochondrial function.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2009.12.088" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2009.12.088</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Drug Design
2010
Animals
Barnes Kendra F
Binding Sites/drug effects/physiology
Bioorganic & medicinal chemistry letters
Carroll Richard T
Dose-Response Relationship
Drug
Drug Delivery Systems/*methods
Funk Max O
Geldenhuys Werner J
Liver/drug effects/metabolism
Mitochondria
Mitochondrial Proteins/*metabolism
Protein Structure
Rats
Secondary
Structure-Activity Relationship
Thiazolidinediones/administration & dosage/*chemical synthesis/*metabolism
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2010.01.140" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2010.01.140</a>
Pages
1918–1923
Issue
6
Volume
20
Dublin Core
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Title
A name given to the resource
3D-QSAR and docking studies on transforming growth factor (TGF)-beta receptor 1 antagonists.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2010
2010-03
Subject
The topic of the resource
Models; Molecular; Quantitative Structure-Activity Relationship; Receptors; Transforming Growth Factor beta/*antagonists & inhibitors
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Nakamura Hiroshi
Description
An account of the resource
The transforming growth factor-beta (TGF-beta) is part of a family of cytokines which regulate various signaling pathways such as cell development, growth, and tissue injury. Although several studies have been published describing the synthesis of small compounds which inhibit the receptor of TGF-beta, especially the subtype 1 receptor (TGBR1) kinase, no 3D-quantitiative structure-activity relationship study has been published. Here we describe the development of a comparative molecular field analysis (CoMFA) model which yielded a partial least squares statistical cross validated r(2) of \textgreater0.3. CoMFA maps agree with docking studies and pharmacophore analysis that hydrogen bonding is important for binding to ALK-5. These studies could enable the medicinal chemist to develop novel inhibitors which can be used in glaucoma filtration surgery.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2010.01.140" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2010.01.140</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2010
Bioorganic & medicinal chemistry letters
Geldenhuys Werner J
Models
Molecular
Nakamura Hiroshi
Quantitative Structure-Activity Relationship
Receptors
Transforming Growth Factor beta/*antagonists & inhibitors
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2010.06.090" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2010.06.090</a>
Pages
4870–4877
Issue
16
Volume
20
Dublin Core
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Title
A name given to the resource
3-D-QSAR and docking studies on the neuronal choline transporter.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2010
2010-08
Subject
The topic of the resource
Binding Sites; Blood-Brain Barrier/metabolism; Computer Simulation; Membrane Transport Proteins/*chemistry/metabolism; Models; Molecular; Neurons/*metabolism; Quantitative Structure-Activity Relationship; Quaternary Ammonium Compounds/chemistry
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Allen David D; Lockman Paul R
Description
An account of the resource
The high affinity neuronal choline transporter (CHT1) is responsible for the uptake of choline into the pre-synaptic terminal of cholinergic neurons. Considering our past experience with modeling the blood-brain barrier choline transporter (BBBCHT) as drug delivery vector to the CNS, we investigated the
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2010.06.090" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2010.06.090</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2010
Allen David D
Binding Sites
Bioorganic & medicinal chemistry letters
Blood-Brain Barrier/metabolism
Computer Simulation
Geldenhuys Werner J
Lockman Paul R
Membrane Transport Proteins/*chemistry/metabolism
Models
Molecular
Neurons/*metabolism
Quantitative Structure-Activity Relationship
Quaternary Ammonium Compounds/chemistry
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2010.06.128" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2010.06.128</a>
Pages
5295–5298
Issue
17
Volume
20
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Identification of novel monoamine oxidase B inhibitors by structure-based virtual screening.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2010
2010-09
Subject
The topic of the resource
Models; Molecular; Monoamine Oxidase Inhibitors/chemistry/*pharmacology; Monoamine Oxidase/*drug effects; Structure-Activity Relationship
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Darvesh Altaf S; Funk Max O; Van der Schyf Cornelis J; Carroll Richard T
Description
An account of the resource
Parkinson's disease is a severe debilitating neurodegenerative disorder. Recently, it was shown that the peroxisome proliferating-activator receptor-gamma agonist pioglitazone protected mice from
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2010.06.128" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2010.06.128</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2010
Bioorganic & medicinal chemistry letters
Carroll Richard T
Darvesh Altaf S
Department of Pharmaceutical Sciences
Funk Max O
Geldenhuys Werner J
Models
Molecular
Monoamine Oxidase Inhibitors/chemistry/*pharmacology
Monoamine Oxidase/*drug effects
NEOMED College of Pharmacy
Structure-Activity Relationship
Van der Schyf Cornelis J
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2011.06.060" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2011.06.060</a>
Pages
4798–4803
Issue
16
Volume
21
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Structure-activity relationship and docking studies of thiazolidinedione-type compounds with monoamine oxidase B.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2011
2011-08
Subject
The topic of the resource
Animals; Humans; Inbred C57BL; Male; Mice; Models; Molecular; Molecular Structure; Monoamine Oxidase Inhibitors/chemical synthesis/chemistry/*pharmacology; Monoamine Oxidase/*metabolism; Stereoisomerism; Structure-Activity Relationship; Thiazolidinediones/chemical synthesis/chemistry/*pharmacology
Creator
An entity primarily responsible for making the resource
Carroll Richard T; Dluzen Dean E; Stinnett Hilary; Awale Prabha S; Funk Max O; Geldenhuys Werner J
Description
An account of the resource
The neuroprotective activity of pioglitazone and rosiglitazone in the MPTP parkinsonian mouse prompted us to evaluate a set of thiazolidinedione (TZD) type compounds for monoamine oxidase A and B inhibition activity. These compounds were able to inhibit MAO-B over several log units of magnitude (82 nM to 600 muM). Initial structure-activity relationship studies identified key areas to modify the aromatic substituted TZD compounds. Primarily, substitutions on the aromatic group and the TZD nitrogen were key areas where activity was enhanced within this group of compounds.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2011.06.060" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2011.06.060</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2011
Animals
Awale Prabha S
Bioorganic & medicinal chemistry letters
Carroll Richard T
Dluzen Dean E
Funk Max O
Geldenhuys Werner J
Humans
Inbred C57BL
Male
Mice
Models
Molecular
Molecular Structure
Monoamine Oxidase Inhibitors/chemical synthesis/chemistry/*pharmacology
Monoamine Oxidase/*metabolism
Stereoisomerism
Stinnett Hilary
Structure-Activity Relationship
Thiazolidinediones/chemical synthesis/chemistry/*pharmacology
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2011.06.111" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2011.06.111</a>
Pages
5498–5501
Issue
18
Volume
21
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
A novel binding assay identifies high affinity ligands to the rosiglitazone binding site of mitoNEET.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2011
2011-09
Subject
The topic of the resource
Binding Sites/drug effects; Dose-Response Relationship; Drug; Ligands; Mitochondrial Proteins/*antagonists & inhibitors/metabolism; Molecular Structure; Recombinant Proteins/antagonists & inhibitors/metabolism; Rosiglitazone; Stereoisomerism; Structure-Activity Relationship; Thiazolidinediones/chemical synthesis/chemistry/*pharmacology
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Funk Max O; Awale Prabha S; Lin Li; Carroll Richard T
Description
An account of the resource
A novel outer mitochondrial membrane protein containing [2Fe-2S] clusters, mitoNEET was first identified through its binding to the anti-diabetic drug pioglitazone. Pioglitazone belongs to a family of drugs that are peroxisome proliferator-activated receptor (PPAR) gamma agonists, collectively known as glitazones. With the lack of pharmacological tools available to fully elucidate mitoNEET's function, we developed a binding assay to probe the glitazone binding site with the aim of developing selective and high affinity compounds. We used multiple thiazolidine-2,4-dione (TZD), 2-thioxothiazolidin-4-one (TTD), and
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2011.06.111" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2011.06.111</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2011
Awale Prabha S
Binding Sites/drug effects
Bioorganic & medicinal chemistry letters
Carroll Richard T
Dose-Response Relationship
Drug
Funk Max O
Geldenhuys Werner J
Ligands
Lin Li
Mitochondrial Proteins/*antagonists & inhibitors/metabolism
Molecular Structure
Recombinant Proteins/antagonists & inhibitors/metabolism
Rosiglitazone
Stereoisomerism
Structure-Activity Relationship
Thiazolidinediones/chemical synthesis/chemistry/*pharmacology
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2011.10.014" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2011.10.014</a>
Pages
7405–7411
Issue
24
Volume
21
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
3D-Quantitative structure-activity relationship and docking studies of the tachykinin NK3 receptor.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2011
2011-12
Subject
The topic of the resource
*Quantitative Structure-Activity Relationship; Binding Sites; Computer Simulation; Drug Design; Humans; Ligands; Models; Molecular; Neurokinin-3/*chemistry/metabolism; Protein Structure; Quinolines/chemistry; Receptors; Tertiary
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Simmons Mark A
Description
An account of the resource
The tachykinin NK(3) receptor (NK(3)R) is a novel drug target for schizophrenia and drug abuse. Since few non-peptide antagonists of this G protein-coupled receptor are available, we have initiated this study to gain a better understanding of the structure-activity relationships of NK(3) antagonist compounds. We developed a 3D comparative molecular similarity index analysis (CoMSIA) model that gave cross-validated PLS values with q(2) \textgreater0.5 which were validated using a test set. We also describe the development of a homology model of the NK(3)R. The model was then used to develop a pharmacophore for docked ligands. This pharmacophore showed two aromatic, two hydrogen donor and one acceptor/aromatic points. These data will be useful for future structure-based drug discovery of ligands for the NK(3)R.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2011.10.014" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2011.10.014</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Quantitative Structure-Activity Relationship
2011
Binding Sites
Bioorganic & medicinal chemistry letters
Computer Simulation
Drug Design
Geldenhuys Werner J
Humans
Ligands
Models
Molecular
Neurokinin-3/*chemistry/metabolism
Protein Structure
Quinolines/chemistry
Receptors
Simmons Mark A
Tertiary
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2011.12.056" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2011.12.056</a>
Pages
1380–1383
Issue
3
Volume
22
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
A scaffold hopping approach to identify novel monoamine oxidase B inhibitors.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2012
2012-02
Subject
The topic of the resource
*Monoamine Oxidase/chemistry/metabolism; Benzofurans/chemistry/pharmacology; Enzyme Activation/drug effects; Flavonoids/chemistry/pharmacology; Humans; Inhibitory Concentration 50; Models; Molecular; Molecular Structure; Monoamine Oxidase Inhibitors/*chemistry/*pharmacology; Protein Binding/drug effects; Small Molecule Libraries; Structure-Activity Relationship
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Funk Max O; Van der Schyf Cornelis J; Carroll Richard T
Description
An account of the resource
Monoamine oxidase B (MAO-B) inhibitors are used to treat Parkinson's disease. In this study, we searched for novel MAO-B inhibitors using a scaffold hopping approach based on our experience with the thiazolidinedione (TZD) class of compounds as MAO-B inhibitors. Several novel compounds were identified, with potencies in the low nanomolar and low micromolar range. We also found that derivatives of the natural product sulfuretin are potent MAO-A and MAO-B inhibitors.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2011.12.056" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2011.12.056</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Monoamine Oxidase/chemistry/metabolism
2012
Benzofurans/chemistry/pharmacology
Bioorganic & medicinal chemistry letters
Carroll Richard T
Enzyme Activation/drug effects
Flavonoids/chemistry/pharmacology
Funk Max O
Geldenhuys Werner J
Humans
Inhibitory Concentration 50
Models
Molecular
Molecular Structure
Monoamine Oxidase Inhibitors/*chemistry/*pharmacology
Protein Binding/drug effects
Small Molecule Libraries
Structure-Activity Relationship
Van der Schyf Cornelis J
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2012.06.096" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2012.06.096</a>
Pages
5675–5678
Issue
17
Volume
22
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Identification of a novel serum and glucocorticoid regulated kinase-1 (SGK1) ligand from virtual screening.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2012
2012-09
Subject
The topic of the resource
Binding Sites; Drug Discovery; Humans; Immediate-Early Proteins/*antagonists & inhibitors/chemistry/metabolism; Ligands; Molecular Docking Simulation; Protein Kinase Inhibitors/*chemistry/*pharmacology; Protein-Serine-Threonine Kinases/*antagonists & inhibitors/chemistry/metabolism
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Talasila Phani K; Sadana Prabodh
Description
An account of the resource
The serum and glucocorticoid regulated kinase-1 (SGK1) is part of the serine/threonine kinase family and has therapeutic potential in several neurodegenerative diseases such as ischemic stroke and Parkinson's disease. Here we use structure-based virtual screening to identify a novel ligand which inhibits SGK1 activity. The data presented here can be used for future scaffold hopping and possible drug development efforts.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2012.06.096" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2012.06.096</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2012
Binding Sites
Bioorganic & medicinal chemistry letters
Department of Pharmaceutical Sciences
Department of Pharmacy Practice
Drug Discovery
Geldenhuys Werner J
Humans
Immediate-Early Proteins/*antagonists & inhibitors/chemistry/metabolism
Ligands
Molecular Docking Simulation
NEOMED College of Graduate Studies
NEOMED College of Pharmacy
Protein Kinase Inhibitors/*chemistry/*pharmacology
Protein-Serine-Threonine Kinases/*antagonists & inhibitors/chemistry/metabolism
Sadana Prabodh
Talasila Phani K
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2012.09.056" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2012.09.056</a>
Pages
7183–7188
Issue
23
Volume
22
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Inhibition of monoamine oxidase by derivatives of piperine, an alkaloid from the pepper plant Piper nigrum, for possible use in Parkinson's disease.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2012
2012-12
Subject
The topic of the resource
Alkaloids/*chemistry/isolation & purification/pharmacology; Animals; Benzodioxoles/*chemistry/isolation & purification/pharmacology; Binding Sites; Blood-Brain Barrier/drug effects; Bovine/metabolism; Cattle; Humans; Hydrogen Bonding; Molecular Docking Simulation; Monoamine Oxidase Inhibitors/*chemistry/isolation & purification/pharmacology; Monoamine Oxidase/*chemistry/metabolism; Parkinson Disease/metabolism/pathology; Piper nigrum/*chemistry; Piperidines/*chemistry/isolation & purification/pharmacology; Polyunsaturated Alkamides/*chemistry/isolation & purification/pharmacology; Protein Binding; Protein Structure; Serum Albumin; Tertiary
Creator
An entity primarily responsible for making the resource
Al-Baghdadi Osamah B; Prater Natalie I; Van der Schyf Cornelis J; Geldenhuys Werner J
Description
An account of the resource
A series of compounds related to piperine and antiepilepsirine was screened in a monoamine oxidase A and B assay. Piperine is an alkaloid from the source plant of both black and white pepper grains, Piper nigrum. Piperine has been shown to have a wide range of activity, including MAO inhibitory activity. The z-factor for the screening assay was found to be greater than 0.8 for both assays. Notably, the compounds tested were selective towards MAO-B, with the most potent compound having an IC(50) of 498 nM. To estimate blood-brain barrier (BBB) permeability, we used a PAMPA assay, which suggested that the compounds are likely to penetrate the BBB. A fluorescent bovine serum albumin (BSA) high-throughput screening (HTS) binding assay showed an affinity of 8 muM for piperine, with more modest binding for other test compounds. Taken together, the data described here may be useful in gaining insight towards the design of selective MAO-B inhibitory compounds devoid of MAO-A activity.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2012.09.056" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2012.09.056</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2012
Al-Baghdadi Osamah B
Alkaloids/*chemistry/isolation & purification/pharmacology
Animals
Benzodioxoles/*chemistry/isolation & purification/pharmacology
Binding Sites
Bioorganic & medicinal chemistry letters
Blood-Brain Barrier/drug effects
Bovine/metabolism
Cattle
Geldenhuys Werner J
Humans
Hydrogen Bonding
Molecular Docking Simulation
Monoamine Oxidase Inhibitors/*chemistry/isolation & purification/pharmacology
Monoamine Oxidase/*chemistry/metabolism
Parkinson Disease/metabolism/pathology
Piper nigrum/*chemistry
Piperidines/*chemistry/isolation & purification/pharmacology
Polyunsaturated Alkamides/*chemistry/isolation & purification/pharmacology
Prater Natalie I
Protein Binding
Protein Structure
Serum Albumin
Tertiary
Van der Schyf Cornelis J
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2013.01.069" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2013.01.069</a>
Pages
1707–1711
Issue
6
Volume
23
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
3D-QSAR and docking studies of pentacycloundecylamines at the sigma-1 (sigma1) receptor.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2013
2013-03
Subject
The topic of the resource
*Quantitative Structure-Activity Relationship; Amines/*chemistry/metabolism; Aza Compounds/chemistry; Binding Sites; Kinetics; Molecular Docking Simulation; Protein Binding; Protein Structure; Receptors; sigma/*chemistry/metabolism; Tertiary
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Novotny Nicholas; Malan Sarel F; Van der Schyf Cornelis J
Description
An account of the resource
Pentacycloundecylamine (PCU) derived compounds have been shown to be promising lead structures for the development of novel drug candidates aimed at a variety of neurodegenerative and psychiatric diseases. Here we show for the first time a 3D quantitative structure-activity relationship (3D-QSAR) for a series of aza-PCU-derived compounds with activity at the sigma-1 (sigma1) receptor. A comparative molecular field analysis (CoMFA) model was developed with a partial least squares cross validated (q(2)) regression value of 0.6, and a non-cross validated r(2) of 0.9. The CoMFA model was effective at predicting the sigma-1 activities of a test set with an r(2) \textgreater0.7. We also describe here the docking of the PCU-derived compounds into a homology model of the sigma-1 (sigma1) receptor, which was developed to gain insight into binding of these cage compounds to the receptor. Based on docking studies we evaluated in a [(3)H]pentazocine binding assay an oxa-PCU, NGP1-01 (IC50=1.78muM) and its phenethyl derivative (IC50=1.54muM). Results from these studies can be used to develop new compounds with specific affinity for the sigma-1(sigma1) receptor.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2013.01.069" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2013.01.069</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Quantitative Structure-Activity Relationship
2013
Amines/*chemistry/metabolism
Aza Compounds/chemistry
Binding Sites
Bioorganic & medicinal chemistry letters
Geldenhuys Werner J
Kinetics
Malan Sarel F
Molecular Docking Simulation
Novotny Nicholas
Protein Binding
Protein Structure
Receptors
sigma/*chemistry/metabolism
Tertiary
Van der Schyf Cornelis J
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2014.03.021" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2014.03.021</a>
Pages
2163–2167
Issue
9
Volume
24
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
A novel Lipoprotein lipase (LPL) agonist rescues the enzyme from inhibition by angiopoietin-like 4 (ANGPTL4).
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2014
2014-05
Subject
The topic of the resource
Angiopoietin-like 4 Protein; Angiopoietins/*metabolism; ANGPTL4; Atherosclerosis; Benzamides/pharmacology; Drug Discovery; Enzyme Activation/*drug effects; High-throughput screen; Homology model; Humans; Ibrolipim; Lipoprotein Lipase/*metabolism; LPL; Molecular Docking Simulation; NO-1886; Organophosphorus Compounds/pharmacology
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Aring Danielle; Sadana Prabodh
Description
An account of the resource
Lipoprotein lipase (LPL) is a key physiological regulator of triglycerides and atherosclerosis risk. Random screening identified a compound designated C10, showing greater LPL agonist activity than NO-1886, a known LPL agonist. Structure-activity relationship (SAR) exploration of C10 led to the identification of C10d exhibiting at least two fold greater LPL activation than
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2014.03.021" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2014.03.021</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2014
Angiopoietin-like 4 Protein
Angiopoietins/*metabolism
ANGPTL4
Aring Danielle
Atherosclerosis
Benzamides/pharmacology
Bioorganic & medicinal chemistry letters
Department of Pharmaceutical Sciences
Department of Pharmacy Practice
Drug Discovery
Enzyme Activation/*drug effects
Geldenhuys Werner J
High-throughput screen
Homology model
Humans
Ibrolipim
Lipoprotein Lipase/*metabolism
LPL
Molecular Docking Simulation
NEOMED College of Graduate Studies
NEOMED College of Pharmacy
NO-1886
Organophosphorus Compounds/pharmacology
Sadana Prabodh
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2014.07.072" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2014.07.072</a>
Pages
4553–4556
Issue
18
Volume
24
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Screening and identification of novel compounds with potential anti-proliferative effects on gallium-resistant lung cancer through an AXL kinase pathway.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2014
2014-09
Subject
The topic of the resource
Antineoplastic Agents/chemical synthesis/chemistry/*pharmacology; Antitumor; AXL; Cell Line; Cell Proliferation/drug effects; Cell Survival/drug effects; Dose-Response Relationship; Drug; Drug Resistance; Drug Screening Assays; Gallium; Gallium-resistance; Gallium/pharmacology; Humans; Lung cancer; Lung Neoplasms/drug therapy/*enzymology/*pathology; Molecular Structure; Naphthalenes/chemistry/*pharmacology; Neoplasm/drug effects; Proto-Oncogene Proteins/*antagonists & inhibitors/metabolism; Pyrazoles/chemistry/*pharmacology; Quinolines/chemistry/*pharmacology; Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism; Structure-Activity Relationship; Tetrazoles/chemistry/*pharmacology; Tumor; Virtual screening
Creator
An entity primarily responsible for making the resource
Oyewumi Moses O; Alazizi Adnan; Liva Sophia; Lin Li; Geldenhuys Werner J
Description
An account of the resource
The clinical application of gallium compounds as anticancer agents is hampered by development of resistance. As a potential strategy to overcome the limitation, eight series of compounds were identified through virtual screening of AXL kinase homology model. Anti-proliferative studies were carried using gallium-sensitive (S) and gallium-resistant (R) human lung adenocarcinoma (A549) cells. Compounds 5476423 and 7919469 were identified as leads. The IC50 values from treating
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2014.07.072" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2014.07.072</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2014
Alazizi Adnan
Antineoplastic Agents/chemical synthesis/chemistry/*pharmacology
Antitumor
AXL
Bioorganic & medicinal chemistry letters
Cell Line
Cell Proliferation/drug effects
Cell Survival/drug effects
Department of Pharmaceutical Sciences
Dose-Response Relationship
Drug
Drug Resistance
Drug Screening Assays
Gallium
Gallium-resistance
Gallium/pharmacology
Geldenhuys Werner J
Humans
Lin Li
Liva Sophia
Lung cancer
Lung Neoplasms/drug therapy/*enzymology/*pathology
Molecular Structure
Naphthalenes/chemistry/*pharmacology
NEOMED College of Pharmacy
Neoplasm/drug effects
Oyewumi Moses O
Proto-Oncogene Proteins/*antagonists & inhibitors/metabolism
Pyrazoles/chemistry/*pharmacology
Quinolines/chemistry/*pharmacology
Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism
Structure-Activity Relationship
Tetrazoles/chemistry/*pharmacology
Tumor
Virtual screening
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2016.09.009" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2016.09.009</a>
Pages
5350–5353
Issue
21
Volume
26
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Identification of small molecules that bind to the mitochondrial protein mitoNEET.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-11
Subject
The topic of the resource
*Bioenergetics; *Glitazones; *Mitochondria; *Small Molecule Libraries; *Type II diabetes; Hypoglycemic Agents/chemistry/metabolism; Ligands; Mitochondrial Proteins/*metabolism; Protein Binding; Thiazolidinediones/chemistry/metabolism
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Yonutas Heather M; Morris Daniel L; Sullivan Patrick G; Darvesh Altaf S; Leeper Thomas C
Description
An account of the resource
MitoNEET (CISD1) is a 2Fe-2S iron-sulfur cluster protein belonging to the zinc-finger protein family. Recently mitoNEET has been shown to be a major role player in the mitochondrial function associated with metabolic type diseases such as obesity and cancers. The anti-diabetic drug pioglitazone and rosiglitazone were the first identified ligands to mitoNEET. Since little is known about structural requirements for ligand binding to mitoNEET, we screened a small set of compounds to gain insight into these requirements. We found that the thiazolidinedione (TZD) warhead as seen in rosiglitazone was not an absolutely necessity for binding to mitoNEET. These results will aid in the development of novel compounds that can be used to treat mitochondrial dysfunction seen in several diseases.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2016.09.009" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2016.09.009</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Bioenergetics
*Glitazones
*Mitochondria
*Small Molecule Libraries
*Type II diabetes
2016
Bioorganic & medicinal chemistry letters
Darvesh Altaf S
Department of Pharmaceutical Sciences
Geldenhuys Werner J
Hypoglycemic Agents/chemistry/metabolism
Leeper Thomas C
Ligands
Mitochondrial Proteins/*metabolism
Morris Daniel L
NEOMED College of Pharmacy
Protein Binding
Sullivan Patrick G
Thiazolidinediones/chemistry/metabolism
Yonutas Heather M
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2016.11.053" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2016.11.053</a>
Pages
303–308
Issue
2
Volume
27
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Structure-activity and in vivo evaluation of a novel lipoprotein lipase (LPL) activator.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2017
2017-01
Subject
The topic of the resource
*Diabetes; *High-fat diet; *Homology modeling; *Hyperlipidemia; *Lipoprotein lipase; *Liver cirrhosis; *Obesity; Animals; Benzeneacetamides/chemical synthesis/chemistry/*pharmacology; Dose-Response Relationship; Drug; Imidazoles/chemical synthesis/chemistry/*pharmacology; Lipoprotein Lipase/*metabolism; Mice; Molecular Docking Simulation; Molecular Structure; Structure-Activity Relationship
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Caporoso Joel; Leeper Thomas C; Lee Yoon-Kwang; Lin Li; Darvesh Altaf S; Sadana Prabodh
Description
An account of the resource
Elevated triglycerides (TG) contribute towards increased risk for cardiovascular disease. Lipoprotein lipase (LPL) is an enzyme that is responsible for the metabolism of core triglycerides of very-low density lipoproteins (VLDL) and chylomicrons in the vasculature. In this study, we explored the structure-activity relationships of our lead compound (C10d) that we have previously identified as an LPL agonist. We found that the cyclopropyl moiety of C10d is not absolutely necessary for LPL activity. Several substitutions were found to result in loss of LPL activity. The compound C10d was also tested in vivo for its lipid lowering activity. Mice were fed a high-fat diet (HFD) for four months, and treated for one week at 10mg/kg. At this dose, C10d exhibited in vivo biological activity as indicated by lower TG and cholesterol levels as well as reduced body fat content as determined by ECHO-MRI. Furthermore, C10d also reduced the HFD induced fat accumulation in the liver. Our study has provided insights into the structural and functional characteristics of this novel LPL activator.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2016.11.053" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2016.11.053</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Diabetes
*High-fat diet
*Homology modeling
*Hyperlipidemia
*Lipoprotein lipase
*Liver cirrhosis
*Obesity
2017
Animals
Benzeneacetamides/chemical synthesis/chemistry/*pharmacology
Bioorganic & medicinal chemistry letters
Caporoso Joel
Darvesh Altaf S
Department of Integrative Medical Sciences
Department of Pharmaceutical Sciences
Department of Pharmacy Practice
Dose-Response Relationship
Drug
Geldenhuys Werner J
Imidazoles/chemical synthesis/chemistry/*pharmacology
Lee Yoon-Kwang
Leeper Thomas C
Lin Li
Lipoprotein Lipase/*metabolism
Mice
Molecular Docking Simulation
Molecular Structure
NEOMED College of Graduate Studies
NEOMED College of Medicine
NEOMED College of Pharmacy
Sadana Prabodh
Structure-Activity Relationship
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2017.02.068" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2017.02.068</a>
Pages
2029–2037
Issue
9
Volume
27
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
High-content screen using zebrafish (Danio rerio) embryos identifies a novel kinase activator and inhibitor.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2017
2017-05
Subject
The topic of the resource
*Cancer; *Compound library; *Kinase; *Notochord; *Phenotypic screen; *Somites; *Zebrafish; Animals; Antineoplastic Agents/chemistry/pharmacology; Antitumor/methods; Benzoic Acid/chemistry/pharmacology; Death-Associated Protein Kinases/metabolism; Drug Discovery/*methods; Drug Screening Assays; Embryo; Enzyme Activation/drug effects; Enzyme Activators/*chemistry/*pharmacology; Neoplasms/drug therapy/enzymology; Nonmammalian/*drug effects/enzymology; Protein Kinase Inhibitors/*chemistry/*pharmacology; Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism; Zebrafish Proteins/antagonists & inhibitors/metabolism; Zebrafish/*embryology
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Bergeron Sadie A; Mullins Jackie E; Aljammal Rowaa; Gaasch Briah L; Chen Wei-Chi; Yun June; Hazlehurst Lori A
Description
An account of the resource
In this report we utilized zebrafish (Danio rerio) embryos in a phenotypical high-content screen (HCS) to identify novel leads in a cancer drug discovery program. We initially validated our HCS model using the flavin adenosine dinucleotide (FAD) containing endoplasmic reticulum (ER) enzyme, endoplasmic reticulum oxidoreductase (ERO1) inhibitor EN460. EN460 showed a dose response effect on the embryos with a dose of 10muM being significantly lethal during early embryonic development. The HCS campaign which employed a small library identified a promising lead compound, a naphthyl-benzoic acid derivative coined compound 1 which had significant dosage and temporally dependent effects on notochord and muscle development in zebrafish embryos. Screening a 369 kinase member panel we show that compound 1 is a PIM3 kinase inhibitor (IC50=4.078muM) and surprisingly a DAPK1 kinase agonist/activator (EC50=39.525muM). To our knowledge this is the first example of a small molecule activating DAPK1 kinase. We provide a putative model for increased phosphate transfer in the ATP binding domain when compound 1 is virtually docked with DAPK1. Our data indicate that observable phenotypical changes can be used in future zebrafish screens to identify compounds acting via similar molecular signaling pathways.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2017.02.068" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2017.02.068</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Cancer
*Compound library
*Kinase
*Notochord
*Phenotypic screen
*Somites
*Zebrafish
2017
Aljammal Rowaa
Animals
Antineoplastic Agents/chemistry/pharmacology
Antitumor/methods
Benzoic Acid/chemistry/pharmacology
Bergeron Sadie A
Bioorganic & medicinal chemistry letters
Chen Wei-Chi
Death-Associated Protein Kinases/metabolism
Department of Integrative Medical Sciences
Drug Discovery/*methods
Drug Screening Assays
Embryo
Enzyme Activation/drug effects
Enzyme Activators/*chemistry/*pharmacology
Gaasch Briah L
Geldenhuys Werner J
Hazlehurst Lori A
Mullins Jackie E
NEOMED College of Medicine
Neoplasms/drug therapy/enzymology
Nonmammalian/*drug effects/enzymology
Protein Kinase Inhibitors/*chemistry/*pharmacology
Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism
Yun June
Zebrafish Proteins/antagonists & inhibitors/metabolism
Zebrafish/*embryology
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2018.03.061" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2018.03.061</a>
Pages
1937–1942
Issue
10
Volume
28
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Novel compounds that target lipoprotein lipase and mediate growth arrest in acute lymphoblastic leukemia.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2018
2018-06
Subject
The topic of the resource
*Acute lymphoblastic leukemia; *Cancer; *Co-culture model; *Lipids; *Lipoprotein lipase; *Metabolism; Amides/chemistry/metabolism/pharmacology; Antineoplastic Agents/*chemistry/metabolism/pharmacology; Binding Sites; Cell Line; Cell Proliferation/drug effects; Coculture Techniques; Dyslipidemias/complications/metabolism/pathology; Humans; Lipoprotein Lipase/antagonists & inhibitors/*metabolism; Mesenchymal Stem Cells/cytology/metabolism; Molecular Docking Simulation; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications/metabolism/pathology; Protein Binding; Protein Structure; Serum Albumin/chemistry/metabolism; Tertiary; Tumor
Creator
An entity primarily responsible for making the resource
Nair Rajesh R; Geldenhuys Werner J; Piktel Debbie; Sadana Prabodh; Gibson Laura F
Description
An account of the resource
Over the past decade, the therapeutic strategies employed to treat B-precursor acute lymphoblastic leukemia (ALL) have been progressively successful in treating the disease. Unfortunately, the treatment associated dyslipidemia, either acute or chronic, is very prevalent and a cause for decreased quality of life in the surviving patients. To overcome this hurdle, we tested a series of cylopropanecarboxamides, a family demonstrated to target lipid metabolism, for their anti-leukemic activity in ALL. Several of the compounds tested showed anti-proliferative activity, with one, compound 22, inhibiting both Philadelphia chromosome negative REH and Philadelphia chromosome positive SupB15 ALL cell division. The novel advantage of these compounds is the potential synergy with standard chemotherapeutic agents, while concomitantly blunting the emergence of dyslipidemia. Thus, the cylopropanecarboxamides represent a novel class of compounds that can be potentially used in combination with the present standard-of-care to limit treatment associated dyslipidemia in ALL patients.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2018.03.061" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2018.03.061</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Acute lymphoblastic leukemia
*Cancer
*Co-culture model
*Lipids
*Lipoprotein lipase
*Metabolism
2018
Amides/chemistry/metabolism/pharmacology
Antineoplastic Agents/*chemistry/metabolism/pharmacology
Binding Sites
Bioorganic & medicinal chemistry letters
Cell Line
Cell Proliferation/drug effects
Coculture Techniques
Department of Pharmaceutical Sciences
Department of Pharmacy Practice
Dyslipidemias/complications/metabolism/pathology
Geldenhuys Werner J
Gibson Laura F
Humans
Lipoprotein Lipase/antagonists & inhibitors/*metabolism
Mesenchymal Stem Cells/cytology/metabolism
Molecular Docking Simulation
Nair Rajesh R
NEOMED College of Graduate Studies
NEOMED College of Pharmacy
Piktel Debbie
Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications/metabolism/pathology
Protein Binding
Protein Structure
Sadana Prabodh
Serum Albumin/chemistry/metabolism
Tertiary
Tumor
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.colsurfb.2012.02.005" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.colsurfb.2012.02.005</a>
Pages
259–265
Volume
94
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Effects of gelucire content on stability, macrophage interaction and blood circulation of nanoparticles engineered from nanoemulsions.
Publisher
An entity responsible for making the resource available
Colloids and surfaces. B, Biointerfaces
Date
A point or period of time associated with an event in the lifecycle of the resource
2012
2012-06
Subject
The topic of the resource
Animals; ATP Binding Cassette Transporter; Calorimetry; Differential Scanning; Drug Carriers/*chemical synthesis/pharmacokinetics; Drug Stability; Emulsions/chemistry; Fatty Alcohols/*chemistry; Fourier Transform Infrared; Humans; Inbred BALB C; Macrophages/*drug effects/metabolism; Member 1/metabolism; Mice; Nanoparticles/*chemistry/ultrastructure; Oils/chemistry; Paclitaxel/pharmacokinetics; Particle Size; Polyethylene Glycols/*chemistry; Reactive Oxygen Species/metabolism; Rhodamine 123/metabolism; Spectroscopy; Subfamily B; Water/chemistry
Creator
An entity primarily responsible for making the resource
Wehrung Daniel; Geldenhuys Werner J; Oyewumi Moses O
Description
An account of the resource
The main objective of the study is to investigate the efficacy of Gelucire 44/14 (gelucire) in facilitating formation of cetyl alcohol (CA)-based nanoparticle (NP) and to assess the effects on key NP properties and functions. NPs from oil-in-water nanoemulsion precursors were prepared using binary mixtures of CA and gelucire (CA/gelucire) containing gelucire at 0, 25, 50 and 75% (w/w). The sizes of gelucire-based NPs (128-183 nm) were five times lower than control NPs (made without gelucire). All the NPs (with or without gelucire component) did not activate macrophages as monitored by reactive oxygen species production. Results from differential scanning calorimetry, FT-IR and multimodal light scattering measurements demonstrated the involvement of gelucire component in achieving homogeneous CA/gelucire particle populations that were stable on storage. The
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.colsurfb.2012.02.005" target="_blank" rel="noreferrer noopener">10.1016/j.colsurfb.2012.02.005</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2012
Animals
ATP Binding Cassette Transporter
Calorimetry
Colloids and surfaces. B, Biointerfaces
Department of Pharmaceutical Sciences
Differential Scanning
Drug Carriers/*chemical synthesis/pharmacokinetics
Drug Stability
Emulsions/chemistry
Fatty Alcohols/*chemistry
Fourier Transform Infrared
Geldenhuys Werner J
Humans
Inbred BALB C
Macrophages/*drug effects/metabolism
Member 1/metabolism
Mice
Nanoparticles/*chemistry/ultrastructure
NEOMED College of Pharmacy
Oils/chemistry
Oyewumi Moses O
Paclitaxel/pharmacokinetics
Particle Size
Polyethylene Glycols/*chemistry
Reactive Oxygen Species/metabolism
Rhodamine 123/metabolism
Spectroscopy
Subfamily B
Water/chemistry
Wehrung Daniel
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.drudis.2014.05.001" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.drudis.2014.05.001</a>
Pages
1601–1606
Issue
10
Volume
19
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
mitoNEET as a novel drug target for mitochondrial dysfunction.
Publisher
An entity responsible for making the resource available
Drug Discovery Today
Date
A point or period of time associated with an event in the lifecycle of the resource
2014
2014-10
Subject
The topic of the resource
Animals; Drug Delivery Systems; Energy Metabolism; Humans; Mitochondria/*metabolism; Mitochondrial Proteins/chemistry/*metabolism; Protein Conformation; Thiazolidinediones/pharmacology
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Leeper Thomas C; Carroll Richard T
Description
An account of the resource
Mitochondrial dysfunction plays an important part in the pathology of several diseases, including Alzheimer's disease and Parkinson's disease. Targeting mitochondrial proteins shows promise in treating and attenuating the neurodegeneration seen in these diseases, especially considering their complex and pleiotropic origins. Recently, the mitochondrial protein mitoNEET [also referred to as CDGSH iron sulfur domain 1 (CISD1)] has emerged as the mitochondrial target of thiazolidinedione drugs such as the antidiabetic pioglitazone. In this review, we evaluate the current understanding regarding how mitoNEET regulates cellular bioenergetics as well as the structural requirements for drug compound association with mitoNEET. With a clear understanding of mitoNEET function, it might be possible to develop therapeutic agents useful in several different diseases including neurodegeneration, breast cancer, diabetes and inflammation.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.drudis.2014.05.001" target="_blank" rel="noreferrer noopener">10.1016/j.drudis.2014.05.001</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2014
Animals
Carroll Richard T
Drug Delivery Systems
Drug Discovery Today
Energy Metabolism
Geldenhuys Werner J
Humans
Leeper Thomas C
Mitochondria/*metabolism
Mitochondrial Proteins/chemistry/*metabolism
Protein Conformation
Thiazolidinediones/pharmacology
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.drudis.2016.10.007" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.drudis.2016.10.007</a>
Pages
352–365
Issue
2
Volume
22
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Emerging strategies of targeting lipoprotein lipase for metabolic and cardiovascular diseases.
Publisher
An entity responsible for making the resource available
Drug Discovery Today
Date
A point or period of time associated with an event in the lifecycle of the resource
2017
2017-02
Subject
The topic of the resource
Animals; Cardiovascular Diseases/drug therapy/*enzymology; Humans; Lipoprotein Lipase/chemistry/*metabolism; Metabolic Diseases/drug therapy/*enzymology
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Lin Li; Darvesh Altaf S; Sadana Prabodh
Description
An account of the resource
Although statins and other pharmacological approaches have improved the management of lipid abnormalities, there exists a need for newer treatment modalities especially for the management of hypertriglyceridemia. Lipoprotein lipase (LPL), by promoting hydrolytic cleavage of the triglyceride core of lipoproteins, is a crucial node in the management of plasma lipid levels. Although LPL expression and activity modulation is observed as a pleiotropic action of some the commonly used lipid lowering drugs, the deliberate development of drugs targeting LPL has not occurred yet. In this review, we present the biology of LPL, highlight the LPL modulation property of currently used drugs and review the novel emerging approaches to target LPL.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.drudis.2016.10.007" target="_blank" rel="noreferrer noopener">10.1016/j.drudis.2016.10.007</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2017
Animals
Cardiovascular Diseases/drug therapy/*enzymology
Darvesh Altaf S
Department of Pharmaceutical Sciences
Department of Pharmacy Practice
Drug Discovery Today
Geldenhuys Werner J
Humans
Lin Li
Lipoprotein Lipase/chemistry/*metabolism
Metabolic Diseases/drug therapy/*enzymology
NEOMED College of Graduate Studies
NEOMED College of Pharmacy
Sadana Prabodh
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.ejphar.2009.08.012" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.ejphar.2009.08.012</a>
Pages
38–43
Issue
1
Volume
619
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Effects of a novel dopamine uptake inhibitor upon extracellular dopamine from superfused murine striatal tissue.
Publisher
An entity responsible for making the resource available
European journal of pharmacology
Date
A point or period of time associated with an event in the lifecycle of the resource
2009
2009-10
Subject
The topic of the resource
Animals; Biological Transport/drug effects; Buffers; Calcium Channels/metabolism; Dopamine Plasma Membrane Transport Proteins/metabolism; Dopamine Uptake Inhibitors/*pharmacology; Dopamine/*metabolism; Extracellular Space/*drug effects/*metabolism; In Vitro Techniques; Male; Methamphetamine/pharmacology; Mice; Neostriatum/*cytology/drug effects; PC12 Cells; Perfusion; Potassium Channel Blockers/pharmacology; Potassium Channels; Potassium Chloride/pharmacology; Rats; Voltage-Gated/antagonists & inhibitors
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Bezuidenhout Lois-May; Dluzen Dean E
Description
An account of the resource
The dopamine transporter (DAT) plays an important role in substance abuse, schizophrenia, and dopaminergic toxicity associated with the Parkinsonian animal model toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Accordingly, the DAT serves as a critical component in regulating dopaminergic function in health and disease states. We have been working with a novel cage compound,
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.ejphar.2009.08.012" target="_blank" rel="noreferrer noopener">10.1016/j.ejphar.2009.08.012</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2009
Animals
Bezuidenhout Lois-May
Biological Transport/drug effects
Buffers
Calcium Channels/metabolism
Dluzen Dean E
Dopamine Plasma Membrane Transport Proteins/metabolism
Dopamine Uptake Inhibitors/*pharmacology
Dopamine/*metabolism
European journal of pharmacology
Extracellular Space/*drug effects/*metabolism
Geldenhuys Werner J
In Vitro Techniques
Male
Methamphetamine/pharmacology
Mice
Neostriatum/*cytology/drug effects
PC12 Cells
Perfusion
Potassium Channel Blockers/pharmacology
Potassium Channels
Potassium Chloride/pharmacology
Rats
Voltage-Gated/antagonists & inhibitors
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.freeradbiomed.2016.09.021" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.freeradbiomed.2016.09.021</a>
Pages
10–19
Volume
101
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
4-Hydroxynonenal dependent alteration of TRPV1-mediated coronary microvascular signaling.
Publisher
An entity responsible for making the resource available
Free radical biology & medicine
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-12
Subject
The topic of the resource
*4-Hydroxynonenal; *Coronary regulation; *Lipid peroxidation; *Post-translational modification; *Protein Processing; *Reactive oxygen species; *Signal Transduction; *TRPV1; Action Potentials/drug effects; Aldehydes/antagonists & inhibitors/metabolism/*pharmacology; Animal; Animals; Blood Flow Velocity; Calcium Signaling/drug effects; Capsaicin/*pharmacology; Cardiovascular Agents/*pharmacology; Coronary Circulation/drug effects; Coronary Vessels/metabolism/physiopathology; Cysteine/genetics/metabolism; Diabetes Mellitus/drug therapy/*metabolism/physiopathology; Disease Models; Femoral Artery/metabolism/physiopathology; HEK293 Cells; Humans; Inbred C57BL; Lipid Peroxidation; Male; Mice; Patch-Clamp Techniques; Post-Translational; TRPV Cation Channels/genetics/*metabolism; Vasodilation/drug effects
Creator
An entity primarily responsible for making the resource
DelloStritto Daniel J; Sinharoy Pritam; Connell Patrick J; Fahmy Joseph N; Cappelli Holly C; Thodeti Charles K; Geldenhuys Werner J; Damron Derek S; Bratz Ian N
Description
An account of the resource
We demonstrated previously that TRPV1-dependent regulation of coronary blood flow (CBF) is disrupted in diabetes. Further, we have shown that endothelial TRPV1 is differentially regulated, ultimately leading to the inactivation of TRPV1, when exposed to a prolonged pathophysiological oxidative environment. This environment has been shown to increase lipid peroxidation byproducts including
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.freeradbiomed.2016.09.021" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2016.09.021</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*4-Hydroxynonenal
*Coronary regulation
*Lipid peroxidation
*Post-translational modification
*Protein Processing
*Reactive oxygen species
*Signal Transduction
*TRPV1
2016
Action Potentials/drug effects
Aldehydes/antagonists & inhibitors/metabolism/*pharmacology
Animal
Animals
Blood Flow Velocity
Bratz Ian N
Calcium Signaling/drug effects
Cappelli Holly C
Capsaicin/*pharmacology
Cardiovascular Agents/*pharmacology
Connell Patrick J
Coronary Circulation/drug effects
Coronary Vessels/metabolism/physiopathology
Cysteine/genetics/metabolism
Damron Derek S
DelloStritto Daniel J
Department of Integrative Medical Sciences
Diabetes Mellitus/drug therapy/*metabolism/physiopathology
Disease Models
Fahmy Joseph N
Femoral Artery/metabolism/physiopathology
Free radical biology & medicine
Geldenhuys Werner J
HEK293 Cells
Humans
Inbred C57BL
Lipid Peroxidation
Male
Mice
NEOMED College of Medicine
Patch-Clamp Techniques
Post-Translational
Sinharoy Pritam
Thodeti Charles K
TRPV Cation Channels/genetics/*metabolism
Vasodilation/drug effects
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.jchromb.2013.11.048" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.jchromb.2013.11.048</a>
Pages
141–146
Volume
945-946
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
A quantitative LC-MS/MS method for determination of thiazolidinedione mitoNEET ligand NL-1 in mouse serum suitable for pharmacokinetic studies.
Publisher
An entity responsible for making the resource available
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
Date
A point or period of time associated with an event in the lifecycle of the resource
2014
2014-01
Subject
The topic of the resource
%CV; %RE; 1-methyl-4-phenyl-1; 2; 3; 3-thiazolidine-2; 4-dione; 5-[3; 5-[4-hydroxy-3; 5-di-tert-butyl-4-hydroxyphenyl)methyl]-1; 5-dimethyl-phenyl)methyl]thiazolidine-2; 6-tetrahydropyridine; Animals; Carry-over; Chromatography; High Pressure Liquid/*methods; internal standard; IS; LC-MS/MS; Limit of Detection; LLOQ; lower limit of quantification; Methanol; Mice; mitoNEET; Mouse serum; MPTP; MRM; multiple reaction monitoring; NL-1; NL-2; percent coefficient of variation; peroxisome proliferator activated receptor-gamma; pharmacokinetic; PK; PPAR-gamma; QC; quality control; relative error; relative matrix effect; RME; SD; standard deviation; Tandem Mass Spectrometry/*methods; thiazolidinedione; Thiazolidinedione (TZD); Thiazolidinediones/*blood; TZD
Creator
An entity primarily responsible for making the resource
Pedada Kiran K; Zhou Xiang; Jogiraju Harini; Carroll Richard T; Geldenhuys Werner J; Lin Li; Anderson David J
Description
An account of the resource
Thiazolidinedione (TZD) compounds have shown promise as antidiabetic, antibiotics, antifungal and neuroprotective agents. The mitochondrial effect of a novel mitoNEET ligand, NL-1 {5-[(3,5-di-tert-butyl-4-hydroxyphenyl)methyl]-1,3-thiazolidine-2,4-dione}, and other TZD compounds, is a newly proposed mechanism for the neuroprotective action of these TZD compounds. In this work, a sensitive LC-MS/MS assay has been developed and validated for quantification of NL-1 in mouse serum. Sample preparation involved an acetonitrile protein precipitation procedure with addition of an internal standard NL-2 {5-[(4-hydroxy-3,5-dimethyl-phenyl)methyl]thiazolidine-2,4-dione}. LC-MS/MS analysis utilized a Columbus C-18 HPLC column (2mmx50mm, 5mum). Chromatography employed a multiple step gradient program that featured a steep linear gradient (25-95% in 0.5min) of 15muM ammonium acetate (additive for eliminating carry-over) in 2% methanol mixing with increasing proportions of 100% methanol. The HPLC was interfaced to a QTrap 5500 mass spectrometer (AB Sciex) equipped with an electrospray ionization source used in a negative ionization mode. Multiple reaction monitoring (MRM) of m/z 334–\textgreater263 for NL-1 and m/z 250–\textgreater179 for NL-2 was done. The method had a linear range of at least 1-100ng/mL in serum. The intra-assay and inter-assay percent coefficient of variation (%CV) were less than 4% and accuracies (%RE) ranged from -2.7% to 2.0%. The analytical procedure gave 96-115% absolute extraction recovery of NL-1. The relative matrix effect was measured and found to be insignificant. The analyte in serum was confirmed to be stable during storage and treatment. The method is suitable for pharmacokinetic (PK) studies of the parent drug NL-1 based on the preliminary serum results from dosed NL-1 mouse studies.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.jchromb.2013.11.048" target="_blank" rel="noreferrer noopener">10.1016/j.jchromb.2013.11.048</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
%CV
%RE
1-Methyl-4-phenyl-1
2
2014
3
3-thiazolidine-2
4-dione
5-[3
5-[4-hydroxy-3
5-di-tert-butyl-4-hydroxyphenyl)methyl]-1
5-dimethyl-phenyl)methyl]thiazolidine-2
6-tetrahydropyridine
Anderson David J
Animals
Carroll Richard T
Carry-over
Chromatography
Department of Internal Medicine
Geldenhuys Werner J
High Pressure Liquid/*methods
internal standard
IS
Jogiraju Harini
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
LC-MS/MS
Limit of Detection
Lin Li
LLOQ
lower limit of quantification
Methanol
Mice
mitoNEET
Mouse serum
MPTP
MRM
multiple reaction monitoring
NEOMED College of Medicine
NL-1
NL-2
Pedada Kiran K
percent coefficient of variation
peroxisome proliferator activated receptor-gamma
pharmacokinetic
PK
PPAR-gamma
QC
Quality Control
relative error
relative matrix effect
RME
SD
standard deviation
Tandem Mass Spectrometry/*methods
thiazolidinedione
Thiazolidinedione (TZD)
Thiazolidinediones/*blood
TZD
Zhou Xiang
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.jchromb.2014.05.048" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.jchromb.2014.05.048</a>
Pages
83–89
Volume
963
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Development and validation of an LC-MS/MS method for determination of the L-type voltage-gated calcium channel/NMDA receptor antagonist NGP1-01 in mouse serum.
Publisher
An entity responsible for making the resource available
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
Date
A point or period of time associated with an event in the lifecycle of the resource
2014
2014-07
Subject
The topic of the resource
Animals; Bridged-Ring Compounds/*blood; Calcium Channel Blockers/*blood; Chromatography; LC-MS/MS; Limit of Detection; Liquid/*methods; Mice; Mouse serum; Multifunctional drug; N-Methyl-D-Aspartate/*antagonists & inhibitors; Neuroprotective agent; NGP1-01; Pentacycloundecylamine; Receptors; Reproducibility of Results; Tandem Mass Spectrometry/*methods
Creator
An entity primarily responsible for making the resource
Jogiraju Harini; Zhou Xiang; Gobburi Ashta Lakshmi Prasad; Pedada Kiran K; Geldenhuys Werner J; Van der Schyf Cornelis J; Crish Samuel D; Anderson David J
Description
An account of the resource
NGP1-01 (8-benzylamino-8,11-oxapentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane) is a heterocyclic cage compound with multifunctional calcium channel blocking activity that has been demonstrated to be neuroprotective in several neurodegenerative models. A sensitive internal standard LC-MS/MS method was developed and validated to quantify NGP1-01 in mouse serum. The internal standard (IS) was
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.jchromb.2014.05.048" target="_blank" rel="noreferrer noopener">10.1016/j.jchromb.2014.05.048</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2014
Anderson David J
Animals
Bridged-Ring Compounds/*blood
Calcium Channel Blockers/*blood
Chromatography
Crish Samuel D
Department of Pharmaceutical Sciences
Geldenhuys Werner J
Gobburi Ashta Lakshmi Prasad
Jogiraju Harini
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
LC-MS/MS
Limit of Detection
Liquid/*methods
Mice
Mouse serum
Multifunctional drug
N-Methyl-D-Aspartate/*antagonists & inhibitors
NEOMED College of Pharmacy
Neuroprotective agent
NGP1-01
Pedada Kiran K
Pentacycloundecylamine
Receptors
Reproducibility of Results
Tandem Mass Spectrometry/*methods
Van der Schyf Cornelis J
Zhou Xiang
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.neuint.2012.03.013" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.neuint.2012.03.013</a>
Pages
806–808
Issue
8
Volume
60
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Dimebon attenuates methamphetamine, but not MPTP, striatal dopamine depletion.
Publisher
An entity responsible for making the resource available
Neurochemistry international
Date
A point or period of time associated with an event in the lifecycle of the resource
2012
2012-06
Subject
The topic of the resource
Animals; Corpus Striatum/*drug effects/metabolism; Dopamine/*metabolism; Drug Synergism; Inbred C57BL; Indoles/*pharmacology; Methamphetamine/*pharmacology; Mice
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Darvesh Altaf S; Dluzen Dean E
Description
An account of the resource
Dimebon is an anti-histamine with central nervous system activity. In this report the effects of dimebon as a neuroprotectant in animal models of Parkinson's disease were tested as assessed in methamphetamine- and MPTP-induced striatal dopaminergic toxicity. Dimebon (1mg/kg) administered at 30 min prior to methamphetamine (40mg/kg) significantly reduced the amount of striatal dopamine depletion in mice, without altering the initial methamphetamine-induced increase in body temperature. In contrast, dimebon at either 1 or 25mg/kg administered at 30 min prior to MPTP (35 mg/kg) was unable to prevent MPTP-induced striatal dopamine loss as determined at 7 days post-methamphetamine/MPTP. These data suggest that dimebon may be exerting a neurotoxin specific neuroprotective effect upon the striatal dopaminergic system and may serve as an important tool for discriminating the mechanistic basis of these two dopaminergic neurotoxins.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.neuint.2012.03.013" target="_blank" rel="noreferrer noopener">10.1016/j.neuint.2012.03.013</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2012
Animals
Corpus Striatum/*drug effects/metabolism
Darvesh Altaf S
Department of Pharmaceutical Sciences
Dluzen Dean E
Dopamine/*metabolism
Drug Synergism
Geldenhuys Werner J
Inbred C57BL
Indoles/*pharmacology
Methamphetamine/*pharmacology
Mice
NEOMED College of Pharmacy
Neurochemistry international
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.ntt.2012.03.003" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.ntt.2012.03.003</a>
Pages
338–343
Issue
3
Volume
34
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Markers associated with testosterone enhancement of methamphetamine-induced striatal dopaminergic neurotoxicity.
Publisher
An entity responsible for making the resource available
Neurotoxicology and teratology
Date
A point or period of time associated with an event in the lifecycle of the resource
2012
2012-06
Subject
The topic of the resource
Animals; Biomarkers/metabolism; Blotting; Body Temperature/drug effects; Body Weight/drug effects; Corpus Striatum/*drug effects/metabolism; Dopamine Plasma Membrane Transport Proteins/metabolism; Dopamine/*metabolism; Drug Synergism; HSP70 Heat-Shock Proteins/metabolism; Inbred Strains; Male; Methamphetamine/*toxicity; Mice; Neurotoxicity Syndromes/*etiology/metabolism; Oxidative Stress/drug effects; Testosterone Propionate/*pharmacology; Vesicular Monoamine Transport Proteins/metabolism; Western
Creator
An entity primarily responsible for making the resource
Buletko A Blake; Dluzen Dean E; McDermott Janet L; Darvesh Altaf S; Geldenhuys Werner J
Description
An account of the resource
Intact male CD-1 mice received an injection of testosterone propionate (TP–5 ug), progesterone (P–5 mg), the oil vehicle or remained untreated (control). At 24 hours after hormonal treatments the mice received an injection of methamphetamine (MA–40 mg/kg) and rectal temperatures were measured. At 5 days post-MA, assays were performed to assess effects of these treatments. Maximal increases in body temperatures, that were significantly greater than oil-treated controls, were obtained in TP-treated mice. At 5 days post-MA, maximal weight reductions were obtained with TP-treated mice, while P-treated mice showed no significant decrease between the pre- versus post-MA determinations. Striatal dopamine concentrations showed maximal reductions and heat-shock protein-70 maximal increases in the TP group, with both differing significantly as compared with all other groups. Protein levels of dopamine transporters were significantly decreased in P-treated mice, while vesicular monoamine transporter-2 was significantly decreased in TP-treated mice. Taken together, these results suggest that testosterone exacerbates the deleterious effects of MA within male mice as indicated by a number of markers related to neurotoxicity. The changes in markers as associated with this enhanced neurotoxicity suggest that TP may increase thermal/energy responses and/or oxidative stress to produce this effect.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.ntt.2012.03.003" target="_blank" rel="noreferrer noopener">10.1016/j.ntt.2012.03.003</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2012
Animals
Biomarkers/metabolism
Blotting
Body Temperature/drug effects
Body Weight/drug effects
Buletko A Blake
Corpus Striatum/*drug effects/metabolism
Darvesh Altaf S
Department of Pharmaceutical Sciences
Dluzen Dean E
Dopamine Plasma Membrane Transport Proteins/metabolism
Dopamine/*metabolism
Drug Synergism
Geldenhuys Werner J
HSP70 Heat-Shock Proteins/metabolism
Inbred Strains
Male
McDermott Janet L
Methamphetamine/*toxicity
Mice
NEOMED College of Pharmacy
Neurotoxicity Syndromes/*etiology/metabolism
Neurotoxicology and teratology
Oxidative Stress/drug effects
Testosterone Propionate/*pharmacology
Vesicular Monoamine Transport Proteins/metabolism
Western
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.nurt.2008.10.037" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.nurt.2008.10.037</a>
Pages
175–186
Issue
1
Volume
6
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Polycyclic compounds: ideal drug scaffolds for the design of multiple mechanism drugs?
Publisher
An entity responsible for making the resource available
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
Date
A point or period of time associated with an event in the lifecycle of the resource
2009
2009-01
Subject
The topic of the resource
*Drug Design; Adamantane/chemistry/pharmacology; Animals; Central Nervous System Diseases/*drug therapy; Humans; Molecular Structure; Neuroprotective Agents/chemistry/*pharmacology/therapeutic use; Polycyclic Compounds/*chemistry/pharmacology/therapeutic use; Psychotropic Drugs/chemistry/*pharmacology/therapeutic use; Quantitative Structure-Activity Relationship
Creator
An entity primarily responsible for making the resource
Van der Schyf Cornelis J; Geldenhuys Werner J
Description
An account of the resource
Recently there has been a resurging interest in developing multi-functional drugs to treat diseases with complex pathological mechanisms. Such drug molecules simultaneously target multiple etiologies that have been found to be important modulators in specific diseases. This approach has significant promise and may be more effective than using one compound specific for one drug target or, by a polypharmaceutical approach, using a cocktail of two or more drugs. Polycyclic ring structures are useful as starting scaffolds in medicinal chemistry programs to develop multi-functional drugs, and may also be useful moieties added to existing structures to improve the pharmacokinetic properties of drugs currently used in the clinic or under development. This review attempts to provide a synopsis of current published research to exemplify the use of polycyclic compounds as starting molecules to develop multi-functional drugs.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.nurt.2008.10.037" target="_blank" rel="noreferrer noopener">10.1016/j.nurt.2008.10.037</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Drug Design
2009
Adamantane/chemistry/pharmacology
Animals
Central Nervous System Diseases/*drug therapy
Geldenhuys Werner J
Humans
Molecular Structure
Neuroprotective Agents/chemistry/*pharmacology/therapeutic use
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
Polycyclic Compounds/*chemistry/pharmacology/therapeutic use
Psychotropic Drugs/chemistry/*pharmacology/therapeutic use
Quantitative Structure-Activity Relationship
Van der Schyf Cornelis J
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.pneurobio.2011.04.010" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.pneurobio.2011.04.010</a>
Pages
347–359
Issue
4
Volume
94
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
The emergence of designed multiple ligands for neurodegenerative disorders.
Publisher
An entity responsible for making the resource available
Progress in neurobiology
Date
A point or period of time associated with an event in the lifecycle of the resource
2011
2011-09
Subject
The topic of the resource
*Drug Design; *Ligands; Amyloid beta-Peptides/metabolism; Antiparkinson Agents/therapeutic use; Clinical Trials as Topic; Humans; Molecular Structure; Neurodegenerative Diseases/*drug therapy; Neuroprotective Agents/*therapeutic use
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Youdim Moussa B H; Carroll Richard T; Van der Schyf Cornelis J
Description
An account of the resource
The incidence of neurodegenerative diseases has seen a constant increase in the global population, and is likely to be the result of extended life expectancy brought about by better health care. Despite this increase in the incidence of neurodegenerative diseases, there has been a dearth in the introduction of new disease-modifying therapies that are approved to prevent or delay the onset of these diseases, or reverse the degenerative processes in brain. Mounting evidence in the peer-reviewed literature shows that the etiopathology of these diseases is extremely complex and heterogeneous, resulting in significant comorbidity and therefore unlikely to be mitigated by any drug acting on a single pathway or target. A recent trend in drug design and discovery is the rational design or serendipitous discovery of novel drug entities with the ability to address multiple drug targets that form part of the complex pathophysiology of a particular disease state. In this review we discuss the rationale for developing such multifunctional drugs (also called designed multiple ligands or DMLs), and why these drug candidates seem to offer better outcomes in many cases compared to single-targeted drugs in pre-clinical studies for neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Examples are drawn from the literature of drug candidates that have already reached the market, some unsuccessful attempts, and others that are still in the drug development pipeline.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.pneurobio.2011.04.010" target="_blank" rel="noreferrer noopener">10.1016/j.pneurobio.2011.04.010</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Drug Design
*Ligands
2011
Amyloid beta-Peptides/metabolism
Antiparkinson Agents/therapeutic use
Carroll Richard T
Clinical Trials as Topic
Geldenhuys Werner J
Humans
Molecular Structure
Neurodegenerative Diseases/*drug therapy
Neuroprotective Agents/*therapeutic use
Progress in neurobiology
Van der Schyf Cornelis J
Youdim Moussa B H
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1021/acschemneuro.7b00287" target="_blank" rel="noreferrer noopener">http://doi.org/10.1021/acschemneuro.7b00287</a>
Pages
2759–2765
Issue
12
Volume
8
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
MitoNEET (CISD1) Knockout Mice Show Signs of Striatal Mitochondrial Dysfunction and a Parkinson's Disease Phenotype.
Publisher
An entity responsible for making the resource available
ACS chemical neuroscience
Date
A point or period of time associated with an event in the lifecycle of the resource
2017
2017-12
Subject
The topic of the resource
*aging; *Disease Models; *drug discovery; *mitochondrial dysfunction; *mitoNEET; Animal; Animals; Corpus Striatum/*metabolism/*pathology; Inbred C57BL; Iron-Binding Proteins/genetics/*metabolism; Knockout; Male; Membrane Proteins/genetics/*metabolism; Mice; Mitochondria/*metabolism/*pathology; Parkinson Disease/*metabolism/pathology
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Benkovic Stanley A; Lin Li; Yonutas Heather M; Crish Samuel D; Sullivan Patrick G; Darvesh Altaf S; Brown Candice M; Richardson Jason R
Description
An account of the resource
Mitochondrial dysfunction is thought to play a significant role in neurodegeneration observed in Parkinson's disease (PD), yet the mechanisms underlying this pathology remain unclear. Here, we demonstrate that loss of mitoNEET (CISD1), an iron-sulfur containing protein that regulates mitochondrial bioenergetics, results in mitochondrial dysfunction and loss of striatal dopamine and tyrosine hydroxylase. Mitochondria isolated from mice lacking mitoNEET were dysfunctional as revealed by elevated reactive oxygen species (ROS) and reduced capacity to produce ATP. Gait analysis revealed a shortened stride length and decreased rotarod performance in knockout mice, consistent with the loss of striatal dopamine. Together, these data suggest that mitoNEET KO mice exhibit many of the characteristics of early neurodegeneration in PD and may provide a novel drug discovery platform to evaluate compounds for enhancing mitochondrial function in neurodegenerative disorders.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1021/acschemneuro.7b00287" target="_blank" rel="noreferrer noopener">10.1021/acschemneuro.7b00287</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Aging
*Disease Models
*drug discovery
*mitochondrial dysfunction
*mitoNEET
2017
ACS chemical neuroscience
Animal
Animals
Benkovic Stanley A
Brown Candice M
Corpus Striatum/*metabolism/*pathology
Crish Samuel D
Darvesh Altaf S
Department of Pharmaceutical Sciences
Geldenhuys Werner J
Inbred C57BL
Iron-Binding Proteins/genetics/*metabolism
Knockout
Lin Li
Male
Membrane Proteins/genetics/*metabolism
Mice
Mitochondria/*metabolism/*pathology
NEOMED College of Pharmacy
Parkinson Disease/*metabolism/pathology
Richardson Jason R
Sullivan Patrick G
Yonutas Heather M
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1021/jm1010012" target="_blank" rel="noreferrer noopener">http://doi.org/10.1021/jm1010012</a>
Pages
8080–8088
Issue
22
Volume
53
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Virtual screening to identify novel antagonists for the G protein-coupled NK3 receptor.
Publisher
An entity responsible for making the resource available
Journal of medicinal chemistry
Date
A point or period of time associated with an event in the lifecycle of the resource
2010
2010-11
Subject
The topic of the resource
*Models; *Narcotic Antagonists; *Quantitative Structure-Activity Relationship; Animals; Binding; Calcium Signaling/drug effects; CHO Cells; Competitive; Cricetinae; Cricetulus; Databases; Factual; Humans; Ligands; Molecular; Neurokinin-3/*antagonists & inhibitors/chemistry; Opioid/chemistry; Quinolines/*chemistry/pharmacology; Radioligand Assay; Receptors
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Kuzenko Stephanie R; Simmons Mark A
Description
An account of the resource
The NK(3) subtype of tachykinin receptor is a G protein-coupled receptor that is a potential therapeutic target for several neurological diseases, including schizophrenia. In this study, we have screened compound databases for novel NK(3) receptor antagonists using a virtual screening protocol of similarity analysis. The lead compound for this study was the potent NK(3) antagonist talnetant. Compounds of the quinoline type found in the virtual screen were additionally evaluated in a comparative molecular field analysis model to predict activity a priori to testing in vitro. Selected members of this latter set were tested for their ability to inhibit ligand binding to the NK(3) receptor as well as to inhibit senktide-induced calcium responses in cells expressing the human NK(3) receptor. Two novel compounds were identified that inhibited NK(3) receptor agonist binding, with potencies in the nM range and antagonized NK(3) receptor-mediated increases in intracellular calcium. These results demonstrate the utility of similarity analysis in identifying novel antagonist ligands for neuropeptide receptors.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1021/jm1010012" target="_blank" rel="noreferrer noopener">10.1021/jm1010012</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Models
*Narcotic Antagonists
*Quantitative Structure-Activity Relationship
2010
Animals
Binding
Calcium Signaling/drug effects
CHO Cells
Competitive
Cricetinae
Cricetulus
Databases
Factual
Geldenhuys Werner J
Humans
Journal of medicinal chemistry
Kuzenko Stephanie R
Ligands
Molecular
Neurokinin-3/*antagonists & inhibitors/chemistry
Opioid/chemistry
Quinolines/*chemistry/pharmacology
Radioligand Assay
Receptors
Simmons Mark A
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1038/emm.2016.78" target="_blank" rel="noreferrer noopener">http://doi.org/10.1038/emm.2016.78</a>
Pages
e257–e257
Issue
9
Volume
48
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Osteoactivin inhibition of osteoclastogenesis is mediated through CD44-ERK signaling.
Publisher
An entity responsible for making the resource available
Experimental & molecular medicine
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-09
Subject
The topic of the resource
*MAP Kinase Signaling System; *Signal Transduction; Animals; Cell Differentiation; Cells; Cultured; Eye Proteins/*metabolism; Hyaluronan Receptors/*metabolism; Inbred C57BL; Male; Membrane Glycoproteins/*metabolism; Mice; Osteoclasts/*cytology/metabolism; RANK Ligand/metabolism; Recombinant Proteins/metabolism
Creator
An entity primarily responsible for making the resource
Sondag Gregory R; Mbimba Thomas S; Moussa Fouad M; Novak Kimberly; Yu Bing; Jaber Fatima A; Abdelmagid Samir M; Geldenhuys Werner J; Safadi Fayez F
Description
An account of the resource
Osteoactivin is a heavily glycosylated protein shown to have a role in bone remodeling. Previous studies from our lab have shown that mutation in Osteoactivin enhances osteoclast differentiation but inhibits their function. To date, a classical receptor and a signaling pathway for Osteoactivin-mediated osteoclast inhibition has not yet been characterized. In this study, we examined the role of Osteoactivin treatment on osteoclastogenesis using bone marrow-derived osteoclast progenitor cells and identify a signaling pathway relating to Osteoactivin function. We reveal that recombinant Osteoactivin treatment inhibited osteoclast differentiation in a dose-dependent manner shown by qPCR, TRAP staining, activity and count. Using several approaches, we show that Osteoactivin binds CD44 in osteoclasts. Furthermore, recombinant Osteoactivin treatment inhibited ERK phosphorylation in a CD44-dependent manner. Finally, we examined the role of Osteoactivin on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteolysis in vivo. Our data indicate that recombinant Osteoactivin inhibits RANKL-induced osteolysis in vivo and this effect is CD44-dependent. Overall, our data indicate that Osteoactivin is a negative regulator of osteoclastogenesis in vitro and in vivo and that this process is regulated through CD44 and ERK activation.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1038/emm.2016.78" target="_blank" rel="noreferrer noopener">10.1038/emm.2016.78</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*MAP Kinase Signaling System
*Signal Transduction
2016
Abdelmagid Samir M
Animals
Cell Differentiation
Cells
Cultured
Department of Anatomy & Neurobiology
Experimental & molecular medicine
Eye Proteins/*metabolism
Geldenhuys Werner J
Hyaluronan Receptors/*metabolism
Inbred C57BL
Jaber Fatima A
Male
Mbimba Thomas S
Membrane Glycoproteins/*metabolism
Mice
Moussa Fouad M
NEOMED College of Medicine
Novak Kimberly
Osteoclasts/*cytology/metabolism
RANK Ligand/metabolism
Recombinant Proteins/metabolism
Safadi Fayez F
Sondag Gregory R
Yu Bing
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1074/jbc.M114.598698" target="_blank" rel="noreferrer noopener">http://doi.org/10.1074/jbc.M114.598698</a>
Pages
1936–1951
Issue
4
Volume
290
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Generation and characterization of ATP analog-specific protein kinase Cdelta.
Publisher
An entity responsible for making the resource available
The Journal of biological chemistry
Date
A point or period of time associated with an event in the lifecycle of the resource
2015
2015-01
Subject
The topic of the resource
Adenosine Triphosphate/*analogs & derivatives/*chemistry; Amino Acid; Amino Acid Sequence; Animals; ATP; Catalysis; Cercopithecus aethiops; Chemical Biology; COS Cells; Glutamine/chemistry; Humans; Inbred C57BL; Leucine/chemistry; Lysine/chemistry; Mice; Molecular Sequence Data; Neutrophils/metabolism; Phenylalanine/chemistry; Phosphorylation; Protein Binding; Protein Kinase C (PKC); Protein Kinase C-delta/*metabolism; Protein Phosphorylation; Purines/chemistry; Sequence Homology; Signal Transduction; Stroke; Substrate Specificity; Superoxides/chemistry; Transgenic
Creator
An entity primarily responsible for making the resource
Kumar Varun; Weng Yi-Chinn; Geldenhuys Werner J; Wang Dan; Han Xiqian; Messing Robert O; Chou Wen-Hai
Description
An account of the resource
To better study the role of PKCdelta in normal function and disease, we developed an ATP analog-specific (AS) PKCdelta that is sensitive to specific kinase inhibitors and can be used to identify PKCdelta substrates. AS PKCdelta showed nearly 200 times higher affinity (Km) and 150 times higher efficiency (kcat/Km) than wild type (WT) PKCdelta toward N(6)-(benzyl)-ATP. AS PKCdelta was uniquely inhibited by 1-(tert-butyl)-3-(1-naphthyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1NA-PP1) and
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1074/jbc.M114.598698" target="_blank" rel="noreferrer noopener">10.1074/jbc.M114.598698</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2015
Adenosine Triphosphate/*analogs & derivatives/*chemistry
Amino Acid
Amino Acid Sequence
Animals
ATP
Catalysis
Cercopithecus aethiops
Chemical Biology
Chou Wen-Hai
COS Cells
Geldenhuys Werner J
Glutamine/chemistry
Han Xiqian
Humans
Inbred C57BL
Kumar Varun
Leucine/chemistry
Lysine/chemistry
Messing Robert O
Mice
Molecular Sequence Data
Neutrophils/metabolism
Phenylalanine/chemistry
Phosphorylation
Protein Binding
Protein Kinase C (PKC)
Protein Kinase C-delta/*metabolism
Protein Phosphorylation
Purines/chemistry
Sequence Homology
Signal Transduction
stroke
Substrate Specificity
Superoxides/chemistry
The Journal of biological chemistry
Transgenic
Wang Dan
Weng Yi-Chinn
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1093/chromsci/bmr055" target="_blank" rel="noreferrer noopener">http://doi.org/10.1093/chromsci/bmr055</a>
Pages
271–276
Issue
3
Volume
50
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Development and validation of a novel RP-HPLC method for the analysis of reduced glutathione.
Publisher
An entity responsible for making the resource available
Journal of chromatographic science
Date
A point or period of time associated with an event in the lifecycle of the resource
2012
2012-03
Subject
The topic of the resource
Chromatography; Glutathione/*analysis; High Pressure Liquid/*methods; Limit of Detection; Linear Models; Nanoparticles/chemistry; Pharmaceutical Preparations/chemistry; Reproducibility of Results; Reverse-Phase/*methods; Spectrophotometry; Ultraviolet
Creator
An entity primarily responsible for making the resource
Sutariya Vijaykumar; Wehrung Daniel; Geldenhuys Werner J
Description
An account of the resource
The objective of this study was the development, optimization, and validation of a novel reverse-phase high-pressure liquid chromatography (RP-HPLC) method for the quantification of reduced glutathione in pharmaceutical formulations utilizing simple UV detection. The separation utilized a C18 column at room temperature and UV absorption was measured at 215 nm. The mobile phase was an isocratic flow of a 50/50 (v/v) mixture of water (pH 7.0) and acetonitrile flowing at 1.0 mL/min. Validation of the method assessed the methods ability in seven categories: linearity, range, limit of detection, limit of quantification, accuracy, precision, and selectivity. Analysis of the system suitability showed acceptable levels of suitability in all categories. Likewise, the method displayed an acceptable degree of linearity (r(2) = 0.9994) over a concentration range of 2.5-60 microg/mL. The detection limit and quantification limit were 0.6 and 1.8 microg/mL respectively. The percent recovery of the method was 98.80-100.79%. Following validation the method was employed in the determination of glutathione in pharmaceutical formulations in the form of a conjugate and a nanoparticle. The proposed method offers a simple, accurate, and inexpensive way to quantify reduced glutathione.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1093/chromsci/bmr055" target="_blank" rel="noreferrer noopener">10.1093/chromsci/bmr055</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2012
Chromatography
Geldenhuys Werner J
Glutathione/*analysis
High Pressure Liquid/*methods
Journal of chromatographic science
Limit of Detection
Linear Models
Nanoparticles/chemistry
Pharmaceutical Preparations/chemistry
Reproducibility of Results
Reverse-Phase/*methods
Spectrophotometry
Sutariya Vijaykumar
Ultraviolet
Wehrung Daniel