Identification of a Dual Autophagy and REV-ERB Inhibitor with in Vivo Anticancer Efficacy.

ABSTRACT: The autophagy process appears as a promising target for anticancer interventions. Chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) are the only FDA-approved autophagy flux inhibitors. Although diverse anticancer clinical trials are providing encouraging results, several limitations associated with the need of high dosage and long-term administration of these autophagy inhibitors are also emerging. We showed that the inhibition of REV-ERB, a nuclear receptor regulating circadian rhythm and metabolism, enhances CQ-mediated cancer cell death and identified a class of dual inhibitors of autophagy and REV-ERB displaying an in vitro anticancer activity against diverse tumor cells greatly higher than CQ. Herein, we describe our lead optimization strategy that led to the identif

SUBMITTER: Palomba M 

PROVIDER: S-EPMC10788905 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature