SR 1903

Description: SR 1903 is a modulator of retinoic acid receptor-related orphan receptor gamma (RORgamma) and liver X receptor (LXR).1 It is an inverse agonist of RORgamma (IC50 = ~100 nM in a cell-based reporter assay) and an agonist of LXR. It also binds to peroxisome proliferator-activated receptor gamma (PPARgamma, IC50 = 209 nM) but does not activate it. SR 1903 (10 µM) inhibits LPS-induced expression of triggering receptor expressed on myeloid cells 1 (TREM-1) in RAW 264.7 cells. It also inhibits LPS-induced expression of the LXR target genes IL-6 and IL-33 and increases expression of ABCG1, FASN, and SCD-1 in RAW 264.7 cells. SR 1903 (20 mg/kg twice per day) reduces severity score in a mouse model of collagen-induced arthritis. It reduces blood glucose levels in a glucose tolerance test, serum levels of total cholesterol and LDL, body weight, and fat mass in a mouse model of high-fat diet-induced obesity. Target: Others. Smiles: CC1=C(C2=CC=C(C(C(F)(F)F)(C(F)(F)F)O)C=C2)C=CC(CN3CCN(CC=4C=CN=CC4)CC3)=C1. References: Chang, M.R., Ciesla, A., Strutzenberg, T.S., et al. Unique polypharmacology nuclear receptor modulator blocks inflammatory signaling pathways. ACS Chem. Biol. 14(5), 1051-1062 (2019).