BMS986195 是一个高效的、不可逆的、共价的、选择抑的布鲁顿氏酪氨酸激酶(BTK)的制剂 (IC50:0.1 nM)。

BMS986195 is a potent, covalent inhibitor of Bruton's tyrosine kinase (BTK), >5,000-fold selective over all kinases outside of the Tec family (IC50<1 nM for BTK).

BMS-986195 inactivated BTK in human whole blood with a rapid rate of inactivation (3.5×10^-4 /nM/min) 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.

In mice, a dose as low as 0.5 mg/kg, taken orally (PO) daily (QD), resulted in peak BTK inactivation of 98% after only the second dose. BTK was inactivated to similar levels in whole blood, lymph nodes and spleen in a dose-dependent manner. BMS-986195 demonstrated robust efficacy in murine models of RA including CIA and CAIA, protecting against clinically evident disease, histologic joint damage and bone mineral density loss. In both models, maximal efficacy was observed at doses ≤0.5 mg/kg PO QD, which achieved ≥95% inactivation of BTK in vivo.

1912445-55-6

C20H23FN4O2

370.428

BMS986195

DMSO:100 mg/mL (269.96 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years