Structure-activity relationship-guided development of retinoic acid receptor-related orphan receptor gamma (RORγ)-selective inverse agonists with a ph...
Basic Information
ID: ALA3259582
Journal: Bioorg Med Chem
Title: Structure-activity relationship-guided development of retinoic acid receptor-related orphan receptor gamma (RORγ)-selective inverse agonists with a phenanthridin-6(5H)-one skeleton from a liver X receptor ligand.
Authors: Nishiyama Y, Nakamura M, Misawa T, Nakagomi M, Makishima M, Ishikawa M, Hashimoto Y.
Abstract: Retinoic acid receptor-related orphan receptors (RORs), which belong to the nuclear receptor superfamily, regulate many physiological processes, including hepatic gluconeogenesis, lipid metabolism, immune function and circadian rhythm. Since RORs resemble liver X receptors (LXRs) in the fold structure of their ligand-binding domains, we speculated that ROR-mediated transcription might be modulated by LXR ligands, in line with the multi-template hypothesis. Therefore, we screened our LXR ligand library for compounds with ROR ligand activity and identified a novel ROR ligand with a phenanthridin-6(5H)-one skeleton. Structure-activity relationship studies aimed at separating ROR inverse agonistic activity from LXR-agonistic activity enabled us to develop a series of ROR inverse agonists based on the phenanthridin-6(5H)-one skeleton, including a RORγ-selective inverse agonist.
CiteXplore: 24702856
DOI: 10.1016/j.bmc.2014.03.007
Patent ID: ┄