AMG 47a

AMG 47a is an orally bioavailable inhibitor of Lck, VEGF receptor 2 (VEGFR2/KDR), p38alpha, and JAK3 (IC50s = 0.2, 1, 3, and 72 nM, respectively). It is selective for these kinases over a panel of additional kinases including SYK, JNK1, and PKAbeta (IC50s = 292 to >25,000 nM) but does inhibit Src (IC50 = 2 nM). It decreases IL-2, but not TNF-alpha, production induced by an anti-CD3 antibody in 50% whole blood and inhibits T cell proliferation in vitro in a mixed lymphocyte reaction assay (IC50 = 30 nM). AMG 47a (10, 30, and 100 mg/kg) has anti-inflammatory activity, decreasing production of IL-2 induced by an anti-CD3 antibody in mice. It also decreases levels of mutant oncogene KRASG12V in HeLa cells in a reporter assay when used at a concentration of 1 µM.Formal Name: 4-methyl-3-[2-[[2-(4-morpholinyl)ethyl]amino]-6-quinazolinyl]-N-[3-(trifluoromethyl)phenyl]-benzamide. CAS Number: 882663-88-9. Molecular Formula: C29H28F3N5O2. Formula Weight: 535.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 25 mg/ml, DMSO: 25 mg/ml, Ethanol: 25 mg/ml, Ethanol:PBS (pH 7.2)(1:2): 0.33 mg/ml. lambdamax: 253, 372 nm. SMILES: CC1=CC=C(C(NC2=CC=CC(C(F)(F)F)=C2)=O)C=C1C3=CC(C=N4)=C(C=C3)N=C4NCCN5CCOCC5. InChi Code: InChI=1S/C29H28F3N5O2/c1-19-5-6-21(27(38)35-24-4-2-3-23(17-24)29(30,31)32)16-25(19)20-7-8-26-22(15-20)18-34-28(36-26)33-9-10-37-11-13-39-14-12-37/h2-8,15-18H,9-14H2,1H3,(H,35,38)(H,33,34,36). InChi Key: DVRSTRMZTAPMKO-UHFFFAOYSA-N.