KC-180-2 Exerts Anti-SCLC Effects via Dual Inhibition of Tubulin Polymerization and Src Signaling.

ABSTRACT: In this study, a series of N-benzyl-2-(5-phenylpyridin-2-yl) acetamide-based derivatives were successfully designed and synthesized as anti-cancer agents. KC-180-2 was screened as a potentially leading compound with dual mechanisms of action: Src signaling and tubulin polymerization inhibition. It efficiently suppressed the proliferation of five cancer cell lines (MDA-MB-231, H446, SKOV-3, HepG2, and HT29), with IC₅₀ values ranging from 5 to 188 nM, especially small-cell lung cancer (SCLC) cells (IC₅₀, 5 nM). Correspondingly, it exerted a significant therapeutic effect on the H446 small-cell lung cancer xenograft model, significantly reducing the volume of tumors without obvious toxicity. Mechanistically, this compound significantly inhibited the polymerization

SUBMITTER: Peng J 

PROVIDER: S-EPMC9476193 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature