Identification of a Class of Novel Tubulin Inhibitors

Title

Identification of a Class of Novel Tubulin Inhibitors

Creator

Yi X; Zhong B; Smith K M; Geldenhuys W J; Feng Y; Pink J J; Dowlati A; Xu Y; Zhou A M; Su B

Publisher

Journal of Medicinal Chemistry

Date

2012
2012-04

Description

We previously developed a series of anticancer agents based on cyclooxygenase-2 (COX-2) inhibitor nimesulide as a lead compound. However, the molecular targets of these agents still remain unclear. In this study, we synthesized a biotinylated probe based on a representative molecule of the compound library and performed protein pull-down assays to purify the anticancer targets of the compound. Via proteomic approaches, the major proteins bound to the probe were identified to be tubulin and heat shock protein 27 (Hsp27), and the compound inhibited tubulin polymerization by binding at the colchicine domain. However, the tubulin inhibitory effect of the compound activated the Hsp27 phosphorylation and possibly overrode the direct Hsp27 inhibitory effects, which made it difficult to solely validate the Hsp27 target. Taken together, the compound was a dual ligand of tubulin and Hsp27, inhibited tubulin polymerization, and had the potential to be a class of new chemotherapeutic agents.

Subject

agents; analog jcc76; biological evaluation; breast-cancer cells; halichondrin-b; heat-shock proteins; hsp27 phosphorylation; in-vivo; nimesulide; nonsteroidal antiinflammatory drugs; Pharmacology & Pharmacy; tumor-cells

Identifier

Format

Journal Article

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

3425-3435

Issue

7

Volume

55

Citation

Yi X; Zhong B; Smith K M; Geldenhuys W J; Feng Y; Pink J J; Dowlati A; Xu Y; Zhou A M; Su B, “Identification of a Class of Novel Tubulin Inhibitors,” NEOMED Bibliography Database, accessed January 27, 2021, https://neomed.omeka.net/items/show/7639.

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