BMS 986142 is a Bruton’s tyrosine kinase (BTK) inhibitor (IC50 = 0.5 nM).1 It is greater than 20-fold selective for BTK over a panel of 384 kinases. BMS 986142 inhibits calcium flux in Ramos B cells induced by B cell receptor (BCR) stimulation (IC50 = 9 nM), as well as BCR stimulation-induced proliferation of, and CD86 surface expression in, peripheral B cells (IC50s = 3 and 4 nM, respectively). It inhibits TNF-α production in human peripheral blood mononuclear cells (PBMCs) induced by Fcγ receptor stimulation (IC50 = 3 nM). BMS 986142 (30 mg/kg per day) reduces the percentage of mice with severe proteinuria and increases survival in an NZB/W lupus-prone mouse model. It reduces hind paw tibiotarsal joint bone resorption and inflammation in a mouse model of collagen antibody-induced arthritis (CAIA) when administered at doses of 5 and 20 mg/kg.2
1.Watterson, S.H., De Lucca, G.V., Shi, Q., et al.Discovery of 6-Fluoro-5-(R)-(3-(S)-(8-fluoro-1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-2-methylphenyl)-2-(S)-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide (BMS-986142): A reversible inhibitor of Bruton's tyrosine kinase (BTK) conformationally constrained by two locked atropisomersJ. Med. Chem.59(19)9173-9200(2016) 2.Gillooly, K.M., Pulicicchio, C., Pattoli, M.A., et al.Bruton's tyrosine kinase inhibitor BMS-986142 in experimental models of rheumatoid arthritis enhances efficacy of agents representing clinical standard-of-carePLoS One12(7)e0181782(2017)