Ezetimibe Engineered L14-8 Suppresses Advanced Prostate Cancer by Activating PLK1/TP53-SAT1-Induced Ferroptosis.

ABSTRACT: Androgen receptor signaling inhibitors (ARSIs) have demonstrated a survival benefit in metastatic prostate cancer. However, patients taking these agents inevitably acquire resistance and even develop neuroendocrine prostate cancer (NEPC), in which stage the AR signaling is inactive, and therapies are limited for these lethal cases. Therefore, developing novel treatments independent of the AR signaling pathway is urgently needed. Here it is reported that L14-8, a small molecule is derived and optimized from ezetimibe, a marketed drug primarily used for intestinal cholesterol and phytosterol absorption, significantly suppresses cell growth in advanced prostate cancer by inducing ferroptosis. Mechanistically, L14-8 binds to and promotes the ubiquitin-mediated PLK1 degradation, resulting in an

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12362806 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature