In vitro activity: BMS-986195 is a highly selective and rapidly acting covalent/irreversible inhibitor of Bruton’s Tyrosine Kinase (BTK) with IC50 of<1 nM and robust efficacy at low doses in preclinical models of RA and Lupus Nephritishighly. BMS-986195 acts by covalently modifying an active-site cysteine residue of BTK. It is more than 5000-fold selective for BTK over all kinases outside of the Tec family, and selectivity ranges from 9- to 1010-fold within the Tec family. BMS-986195 inactivated BTK in human whole blood with a rapid rate of inactivation (3.5×10-4 nM-1·min-1) and potently inhibited antigen-dependent interleukin-6 production, CD86 expression and proliferation in B cells (IC50 <1 nM) without effect on antigen-independent measures in the same cells. A similar potency was measured against FcγR-dependent TNF-α production in human cells.

Kinase Assay: BMS-986195 is a highly selective and rapidly acting covalent/irreversible inhibitor of Bruton’s Tyrosine Kinase (BTK) with IC50 of<1 nM and robust efficacy at low doses in preclinical models of RA and Lupus Nephritishighly. BMS-986195 acts by covalently modifying an active-site cysteine residue of BTK. It is more than 5000-fold selective for BTK over all kinases outside of the Tec family, and selectivity ranges from 9- to 1010-fold within the Tec family.

Cell Assay: BMS-986195 inactivates BTK in human whole blood with a rapid rate of inactivation (3.5×10-4nM-1omin-1) and potently inhibits antigen-dependent interleukin-6 production, CD86 expression and proliferation in B cells (IC50<1 nM) without effect on antigen-independent measures in the same cells. A similar potency is measured against FcγR-dependent TNF-α production in human cells.