Novel Synthetic Pharmacophores Inducing a Stabilization of Cellular Microtubules
Gustavo J. Gozzi,
Attilio Di Pietro,
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.
Keywords: Chemical biology, high content analysis, microtubule dynamics, microtubule targeting agents, phenotypic screening.
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