BMS-336 is a potent, selective, orally active RORγt (RORC2) inverse agonist with EC50 of 39 nM in RORγt reporter assays.
BMS-336 displays weak to no activity against PXR, LXRα an d LXRβ.
BMS-336 (p.o.) significantly blocked the IL-17 response in a dose-dependent manner and achieved 74% inhibition at 25 mg/kg and 98% inhibition at 100 mg/kg doses, respectively.
BMS-336 inhibited expression of RORC2-regulated genes in peripheral Th17 cells (CD4+CD25-CD127+CXCR3-CCR4+CCR6+) in a dose-dependent manner, with similar inhibitory effects on laminar propria mononuclear cells from IBD and non-IBD subjects.
BMS-336 inhibited IL-17A production and prevented inflammatory cytokine-induced destabilization in peripheral Th17-Tregs (CD4+CD25hiCD127loCXCR3-CCR4+CCR6+).
