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ID: ALA5226354

Journal: J Med Chem

Title: The Medicinal Chemistry and Therapeutic Potential of LRH-1 Modulators.

Authors: Lang A, Isigkeit L, Schubert-Zsilavecz M, Merk D.

Abstract: The ligand-activated transcription factor liver receptor homologue 1 (LRH-1, NR5A2) is involved in the regulation of metabolic homeostasis, including cholesterol and glucose balance. Preliminary evidence points to therapeutic potential of LRH-1 modulation in diabetes, hepatic diseases, inflammatory bowel diseases, atherosclerosis, and certain cancers, but because of a lack of suitable ligands, pharmacological control of LRH-1 has been insufficiently studied. Despite the availability of considerable structural knowledge on LRH-1, only a few ligand chemotypes have been developed, and potent, selective, and bioavailable tools to explore LRH-1 modulation in vivo are lacking. In view of the therapeutic potential of LRH-1 in prevalent diseases, improved chemical tools are needed to probe the beneficial and adverse effects of pharmacological LRH-1 modulation in sophisticated preclinical models and to further elucidate the receptor's molecular function.

CiteXplore: 34839661

DOI: 10.1021/acs.jmedchem.1c01663