| Description |
BMS-986143 is an orally active, reversible BTK inhibitor with an IC50 of 0.26 nM. BMS-986143 also inhibits TEC, BLK, BMX, TXK FGR, YES1, ITK with IC50s of 3 nM, 5 nM, 7 nM, 10 nM, 15 nM,19 nM, 21 nM, respectively. BMS-986143 can be used for the research of autoimmune diseases[1].
|
| Related Catalog |
|
| In Vitro |
BMS-986143 inhibits BTK with IC50s of 6.9±3.4 and 25±19 nM in Ramos cellular assay and the human whole blood assay, respectively[1]. BMS-986143 provides potent inhibition of end points derived from IgG-containing immune complex low affinity activating Fcγ receptor signaling in peripheral blood mononuclear cells (PBMC) (IC50=2 nM)[1]. BMS-986143 inhibits the expression of CD63 on the surface of basophils in human whole blood, driven by FcεRI signaling (IC50 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 IC50s of 7±3, 1±0.4, 1±0.5, and 2 nM, respectively[1].
|
| In Vivo |
BMS-986143 demonstrates 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 Cmax (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 IC50 (130 nM).
|
| References |
[1]. Anurag S Srivastava, et al. Driving Potency with Rotationally Stable Atropisomers: Discovery of Pyridopyrimidinedione-Carbazole Inhibitors of BTK. ACS Med Chem Lett. 2020 Sep 16;11(11):2195-2203.
|
