3D-QSAR and docking studies on transforming growth factor (TGF)-beta receptor 1 antagonists.

3D-QSAR and docking studies on transforming growth factor (TGF)-beta receptor 1 antagonists.

Geldenhuys Werner J; Nakamura Hiroshi

Bioorganic & medicinal chemistry letters

2010

2010-03

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.

Models; Molecular; Quantitative Structure-Activity Relationship; Receptors; Transforming Growth Factor beta/*antagonists & inhibitors

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1918–1923

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