BMS-986143, an orally active, reversible BTK inhibitor with an IC50 value of 0.26 nM, is designed for autoimmune disease research. Additionally, it targets TEC, BLK, BMX, TXK, FGR, YES1, and ITK, exhibiting IC50s of 3 nM, 5 nM, 7 nM, 10 nM, 15 nM, 19 nM, and 21 nM, respectively [1].

BMS-986143 inhibits BTK with IC 50 s of 6.9±3.4 and 25±19 nM in Ramos cellular assay and the human whole blood assay, respectively [1]. BMS-986143 can effectively inhibit the end-points derived from IgG-containing immune complex low affinity activating Fcγ receptor signaling in peripheral blood mononuclear cells (PBMC) (IC 50 =2 nM) [1]. BMS-986143 inhibits the expression of CD63 on the surface of basophils in human whole blood, driven by FcεRI signaling (IC 50 of 54 nM) [1]. BMS-986143 inhibits calcium flux in Ramos B Cells, proliferation of human peripheral B Cells, CD86 surface expression in peripheral B Cells, and TNFα from human PBMC Cells with IC 50 s of 7±3, 1±0.4, 1±0.5, and 2 nM, respectively [1].

BMS-986143 shows desirable efficacy in mouse models of collagen-induced arthritis (CIA) and anticollagen antibody-induced arthritis (CAIA) [1]. BMS-986143 exhibits high oral bioavailability (mouse 100%, dog 82%) and moderate C max (mouse 4.3, dog 1.2 μM) following oral administration (mouse 6, dog 2 mg/kg) [1]. BMS-986143 exhibits long elimination half-lives (mouse 3.6, dog 7.9 h) due to moderate plasma clearance (8.6, 4.4 mL/min/kg respectively) combined with low volumes of distribution (1.8, 2.6 L/kg respectively) following intravenous administration (mouse 3.0, dog 1.0 mg/kg) [1]. Animal Model: DBA/1 male mice (8-10wk of age) bearing CIA model [1] Dosage: 15 and 45 mg/kg Administration: Oral gavage; BID Result: 15 and 45 mg/kg provided dose-dependent inhibition of observed clinical disease progression (63% and 80%, respectively), representing 17 and 19 h coverage of the mouse whole blood IC 50 (130 nM).