New High-Throughput Screen Discovers Novel Ligands of Full-Length Nuclear Receptor LRH-1.

ABSTRACT: Nuclear receptor liver receptor homolog-1 (LRH-1, NR5A2) is a lipid-regulated transcription factor and an important drug target for several liver diseases. Advances toward LRH-1 therapeutics have been driven recently by structural biology, with fewer contributions from compound screening. Standard LRH-1 screens detect compound-induced interaction between LRH-1 and a transcriptional coregulator peptide, an approach that excludes compounds that regulate LRH-1 through alternative mechanisms. Here, we developed a FRET-based LRH-1 screen that simply detects compound binding to LRH-1, applying it to discover 58 new compounds that bind the canonical ligand-binding site in LRH-1 (2.5% hit rate), also supported by computational docking. Four independent functional screens identified 15 of th

SUBMITTER: Malabanan MM 

PROVIDER: S-EPMC10404069 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature