Design, Synthesis, and Biological Evaluation of Apcin-Based CDC20 Inhibitors.

ABSTRACT: CDC20 binds to anaphase-promoting complex/cyclosome E3 ubiquitin ligase to recruit substrates for ubiquitination to promote mitotic progression. In breast and other cancers, CDC20 overexpression causes cell cycle dysregulation and is associated with poor prognosis. Apcin was previously discovered as a CDC20 inhibitor exhibiting high micromolar activities. Here, we designed and developed new apcin-based inhibitors by eliminating a controlled substance, chloral hydrate, required for synthesis. We further improved the antitumor activities of the inhibitors by replacing the pyrimidine group with substituted thiazole-containing groups. When evaluated in MDA-MB-231 and MDA-MB-468 triple negative breast cancer cell lines, several analogs showed 5-10-fold improvement over apcin with IC₅₀

SUBMITTER: Bhuniya R 

PROVIDER: S-EPMC8842116 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature