BMS 986165

BMS 986165 is an allosteric inhibitor of tyrosine kinase 2 (TYK2, IC50 = 0.2 nM for the recombinant TYK2 pseudokinase domain). It is selective for TYK2 over a panel of 249 protein and lipid kinases at 1 µM but does inhibit the JAK1 pseudokinase domain and bone morphogenetic protein receptor type II (BMPR2, IC50s = 1 and 193 nM, respectively). BMS 986165 inhibits IFN-alpha-induced phosphorylation of STAT1, -2, -3, and -5 in primary human peripheral blood mononuclear cells (PBMCs, IC50s = 1-6 nM). It also inhibits IL-12-induced production of IFN-gamma in human PBMCs (IC50 = 11 nM) and IL-12-induced phosphorylation of STAT4 in NK-92 cells (IC50 = 5 nM). BMS 986165 (1 and 10 mg/kg) reduces IL-12 and IL-18-induced production of IFN-gamma in mice. It inhibits IFN-regulated expression of IFIT3, IFIT1, and MX1, genes encoding innate antiviral response proteins, and reduces tubulointerstitial and glomerular nephritis in female NZB/W lupus-prone mice. BMS 986165 also inhibits anti-CD40 antibody-induced colitis and systemic wasting in mice.Formal Name: 6-[(cyclopropylcarbonyl)amino]-4-[[2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl]amino]-N-(methyl-d3)-3-pyridazinecarboxamide. CAS Number: 1609392-27-9. Molecular Formula: C20H19D3N8O3. Formula Weight: 425.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 1 mg/ml, DMSO: 1 mg/ml, DMSO:PBS (pH 7.2) (1:2): 0.33 mg/ml. lambdamax: 252 nm. SMILES: COC1=C(C2=NN(C)C=N2)C=CC=C1NC3=C(N=NC(NC(C4CC4)=O)=C3)C(NC([2H])([2H])[2H])=O. InChi Code: InChI=1S/C20H22N8O3/c1-21-20(30)16-14(9-15(25-26-16)24-19(29)11-7-8-11)23-13-6-4-5-12(17(13)31-3)18-22-10-28(2)27-18/h4-6,9-11H,7-8H2,1-3H3,(H,21,30)(H2,23,24,25,29)/i1D3. InChi Key: BZZKEPGENYLQSC-FIBGUPNXSA-N.