3-nitropyridine analogues as novel microtubule-targeting agents.

ABSTRACT: Microtubule-targeting agents are an important class of anti-cancer drugs; their full potential is however not realized because of significant myelotoxicity and neurotoxicity. We here report 3-nitropyridine analogues as a novel group of microtubule-targeting agents with potent anti-cancer effects against a broad range of cancer types. We show that these 3-nitropyridines induce cell cycle arrest in the G2-M phase and inhibit tubulin polymerization by interacting with tubulin. Determination of the tubulin-4AZA2996 structure by X-ray crystallography demonstrated that this class of compounds binds to the colchicine-site of tubulin. Furthermore, the anti-cancer effect was demonstrated both in vitro and in vivo in a murine heterotopic xenograft model of colon cancer. When administered intravenous

SUBMITTER: Herman J 

PROVIDER: S-EPMC11542830 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature