Identification of A Class of Novel Tubulin Inhibitors
Document Type
Article
Publication Date
4-12-2012
Publication Title
Journal of Medicinal Chemistry
Abstract
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.
Recommended Citation
Yi, Xin; Zhong, Bo; Smith, Kerri M.; Geldenhuys, Werner J.; Feng, Ye; Pink, John J.; Dowlati, Afshin; Xu, Yan; Zhou, Aimin; and Su, Bin, "Identification of A Class of Novel Tubulin Inhibitors" (2012). Chemistry Faculty Publications. 255.
https://engagedscholarship.csuohio.edu/scichem_facpub/255
DOI
10.1021/jm300100d
Volume
55
Issue
7
