Uncovering α-Selectivity for Liver X Receptor Agonists for Lipotoxic Cancer Therapies.

ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer-related deaths worldwide. We recently showed that pharmacologically induced lipotoxicity represents a promising therapeutic strategy for the treatment of HCC. Synthetic LXRα agonists induce the production of toxic saturated fatty acids in tumor cells. When combined with DFG-out Raf inhibitors, which block fatty acid desaturation by inducing proteasomal degradation of stearoyl-CoA desaturase (SCD1), LXRα activation can trigger lipotoxicity-induced cancer cell death. However, the clinical translation of this therapeutic strategy is limited by the lack of specific LXRα agonists for clinical use. Here, we have developed a series of promising maleimide LXR agonists with increased potency for LXRα and enhanced specificit

SUBMITTER: Galvez B Pedreira J 

PROVIDER: S-EPMC11997999 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature