BMS-986251 is a potent and specific RORγt inverse agonist that exerts its action via oral administration. It shows an EC 50 of 12 nM for RORγt GAL4. In human whole blood assay, BMS-986251 effectively inhibits IL-17 with an EC 50 of 24 nM. Furthermore, BMS-986251 exhibits strong therapeutic effects in mouse acanthosis and Imiquimod-induced models, which are commonly used preclinical models for psoriasis.

RORβ:>10 μM (EC50), IL-17:24 nM (EC50), RORγt:12 nM (EC50), RORα:>10 μM (EC50)

BMS-986251 is against ROR family members (RORα GAL4: EC 50 >10 μM; RORβ GAL4: EC 50 >10 μM) and against other nuclear receptors (PXR: EC 50 >5 μM; LXRα: EC 50 >7.5 μM; LXRβ: EC 50 >7.5 μM). BMS-986251 does not inhibit any of the CYP’s[1].

BMS-986251 (5-45 mg/kg; orally; twice daily until day 9) results in reduced ear thickness[1]. BMS-986251 (0.13, 0.79, 4.76 mg/kg; orally; once a day) displays a dose-dependent reduction of the IL-17F produced in na?ve C57BL/6 female mice (7-9 weeks)[1]. BMS-986251 (2 mg/kg of IV and 4 mg/kg of PO) has a T 1/2 of 7.7 hours, a CL of 2.7 mL/min?kg, and a V ss of 1.9 L/kg for IV in mouse[1]. Animal Model: C57BL/6 female mice with acanthosis[1]Dosage: 5, 15, 45 mg/kg Administration: Orally; twice daily until day 9 Result: Resulted in reduced ear thickness and significantly reduces imiquimod (IMQ)-induced skin thickening. Animal Model: Mouse or rat[1]Dosage: 2 mg/kg of IV and 4 mg/kg of PO (Pharmacokinetic Analysis) Administration: IV or PO Result: Had a T 1/2 of 7.7 hours, a CL of 2.7 mL/min?kg, and a V ss of 1.9 L/kg for IV in mouse. Had a C max of 4.8 μM and an AUC of 37 μM?h for PO in mouse. Had a T 1/2 of 11 hours, a CL of 1.3 mL/min?kg, and a V ss of 1.25 L/kg for IV in rat. Had a C max of 4.7 μM and an AUC of 64 μM?h for PO in rat.