BMS-986202

BMS-986202 is a potent, selective and orally active Tyk2 inhibitor that binds to Tyk2 JH2 with an IC50 of 0.19 nM and a Ki of 0.02 nM. BMS-986202 is remarkably selective over other kinases including Jak family members. BMS-986202 is also a weak inhibitor of CYP2C19 with an IC50 of 14 μM. BMS-986202 can be used for IL-23-driven acanthosis, anti-CD40-induced colitis, and spontaneous lupus research[1].

BMS-986202 inhibits IFNα and IL-23 in Kit225 T cells with IC50 values of 10 nM and 12 nM, respectively[1].BMS-986202 is potent in the IFNα stimulated STAT5 phosphorylation human whole blood (hWB) assay and mouse whole blood (mWB) with IC50 values of 58 nM and 481 nM, respectively[1].

BMS-986202 (Compound 7; 3-30 mg/kg; p.o.; daily; for 9 days) treatment inhibits IL-23-driven acanthosis in mice[1].BMS-986202 (Compound 7; 0.4-10 mg/kg; p.o.) treatment inhibits IL-12/IL-18-induced IFNγ production in mice. BMS-986202 dose-dependently inhibits IFNγ production by 46% and 80% at doses of 2 mg/kg and 10 mg/kg, respectively[1].BMS-986202 (Compound 7; 7-10 mg/kg; p.o.) is stable in liver microsomes, with half lives of greater than 120 min in mouse, rat, monkey, and humans and 89 min in dog. The serum protein binding for BMS-986202 in these species ranges from 89.3% to 96.0%, leaving a good range of free fraction of drug available. BMS-986202 shows the oral bioavailability up to 62-100%[1].

[1]. Chunjian Liu, et al. Discovery of BMS-986202: A Clinical Tyk2 Inhibitor that Binds to Tyk2 JH2. J Med Chem. 2021 Jan 14;64(1):677-694.