Repositioning VU-0365114 as a novel microtubule-destabilizing agent for treating cancer and overcoming drug resistance.

ABSTRACT: Microtubule-targeting agents represent one of the most successful classes of anticancer agents. However, the development of drug resistance and the appearance of adverse effects hamper their clinical implementation. Novel microtubule-targeting agents without such limitations are urgently needed. By employing a gene expression-based drug repositioning strategy, this study identifies VU-0365114, originally synthesized as a positive allosteric modulator of human muscarinic acetylcholine receptor M5 (M5 mAChR), as a novel type of tubulin inhibitor by destabilizing microtubules. VU-0365114 exhibits a broad-spectrum in vitro anticancer activity, especially in colorectal cancer cells. A tumor xenograft study in nude mice shows that VU-0365114 slowed the in vivo colorectal tumor growth. The antica

SUBMITTER: Hsieh YY 

PROVIDER: S-EPMC10850822 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature