Branebrutinib

Branebrutinib is a covalent inhibitor of Bruton's tyrosine kinase (BTK, IC50 = 0.1 nM). It is greater than 5,000-fold selective for BTK over a panel of 240 kinases but does inhibit the additional Tec family kinases Tec, BMX, and TMX (IC50s = 0.9, 1.5, and 5 nM, respectively). Branebrutinib inhibits calcium flux in Ramos B cells induced by B cell receptor (BCR) stimulation (IC50 = 7.2 nM), as well as BCR stimulation-induced proliferation of, and CD86 surface expression in, peripheral B cells (IC50s = 0.04 and 0.3 nM, respectively). It inhibits TNF-alpha production in human peripheral blood mononuclear cells (PMBCs) induced by Fcgamma receptor stimulation (IC50 = 0.3 nM). Branebrutinib (0.5 mg/kg) is completely protective against bone destruction in a mouse model of collagen-induced arthritis. It also reduces proteinuria and glomerular IgG immune complex deposition and increases survival in an NZB/W lupus-prone mouse model.Formal Name: 5-fluoro-2,3-dimethyl-4-[(3S)-3-[(1-oxo-2-butyn-1-yl)amino]-1-piperidinyl]-1H-indole-7-carboxamide. CAS Number: 1912445-55-6. Synonyms: BMS-986195. Molecular Formula: C20H23FN4O2. Formula Weight: 370.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS (pH 7.2) (1:4): 0.20 mg/ml, Ethanol: 1 mg/ml. lambdamax: 242, 329 nm. SMILES: CC1=C(C)NC2=C(C(N)=O)C=C(F)C(N3C[C@H](CCC3)NC(C#CC)=O)=C12. InChi Code: InChI=1S/C20H23FN4O2/c1-4-6-16(26)24-13-7-5-8-25(10-13)19-15(21)9-14(20(22)27)18-17(19)11(2)12(3)23-18/h9,13,23H,5,7-8,10H2,1-3H3,(H2,22,27)(H,24,26)/t13-/m0/s1. InChi Key: VJPPLCNBDLZIFG-ZDUSSCGKSA-N.