Title:Novel Synthetic Pharmacophores Inducing a Stabilization of Cellular Microtubules
Volume: 15
Issue: 1
Author(s): Anne Martinez, Emmanuelle Soleilhac, Caroline Barette, Renaud Prudent, Gustavo J. Gozzi, Emilie Vassal-Stermann, Catherine Pillet, Attilio Di Pietro, Marie-Odile Fauvarque and Laurence Lafanechere
Affiliation:
关键词:
化学生物学；高内涵细胞成像分析技术；微管动力学；微管靶向剂；表型筛选。
摘要: Microtubule drugs have been widely used in cancer chemotherapies. Although microtubules are
subject to regulation by signal transduction mechanisms, their pharmacological modulation has so far relied
on compounds that bind to the tubulin subunit. Using a cell-based assay designed to probe the microtubule polymerization
status, we identified two pharmacophores, CM09 and CM10, as cell-permeable microtubule stabilizing agents. These
synthetic compounds do not affect the assembly state of purified microtubules in vitro but they profoundly suppress
microtubule dynamics in vivo. Moreover, they exert cytotoxic effects on several cancer cell lines including multidrug
resistant cell lines. Therefore, these classes of compounds represent novel attractive leads for cancer chemotherapy.
