TAS 0728

TAS 0728 is a covalent HER2 inhibitor (IC50 = 36 nM). It is selective for HER2 over panels of 386 and 374 additional kinases, as well as a panel of 68 non-kinase enzymes, when used at a concentration of 1 µM. TAS 0728 inhibits HER2 autophosphorylation in HER2-overexpressing SK-BR-3 cells but not autophosphorylation of EGFR in EGFR-overexpressing A431 cells. It inhibits the growth of six HER2-amplified breast, lung, and gastric cancer cell lines (GI50s = 1.6-31 nM). TAS 0278 (30 and 60 mg/kg) reduces tumor volume in NCI N87 and BT474 mouse xenograft models.Formal Name: 4-amino-N-[4-[2-(dimethylamino)-2-oxoethyl]-2,3-dimethylphenyl]-1-[(3R)-1-(1-oxo-2-propen-1-yl)-3-piperidinyl]-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide. CAS Number: 2088323-16-2. Molecular Formula: C26H32N8O3. Formula Weight: 504.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS (7.2 pH) 1:2: 0.33 mg/ml, Ethanol: 15 mg/ml. SMILES: CC(C(C)=C(C=C1)CC(N(C)C)=O)=C1NC(C2=NN([C@@]3([H])CN(CCC3)C(C=C)=O)C4=NC=NC(N)=C42)=O. InChi Code: InChI=1S/C26H32N8O3/c1-6-20(35)33-11-7-8-18(13-33)34-25-22(24(27)28-14-29-25)23(31-34)26(37)30-19-10-9-17(15(2)16(19)3)12-21(36)32(4)5/h6,9-10,14,18H,1,7-8,11-13H2,2-5H3,(H,30,37)(H2,27,28,29)/t18-/m1/s1. InChi Key: JCCIICHPRAAMGK-GOSISDBHSA-N.