ENMD-2076

ENMD-2076 is a multi-kinase inhibitor that inhibits FMS-related tyrosine kinase 3 (FLT3), RET, and Aurora A kinase with IC50 values of 1.86, 10.4, and 14 nM, respectively. It inhibits additional kinases involved in angiogenesis such as VEGFR3, PDGFRalpha, and FGFR2, among others, with IC50 values of less than 100 nM. It inhibits proliferation of several human triple-negative breast cancer (TNBC) cell lines with IC50 values of less than 1 µM, halts the cell cycle at the G2 phase, and induces apoptosis. Oral administration of ENMD-2076 (200 mg/kg), reduces proliferation, enhances p53- and p73-mediated cancer cell apoptosis and senescence, and inhibits growth of sensitive primary tumors in a TNBC mouse xenograft model. It also decreases tumor vascular permeability and perfusion and inhibits tumor growth in human TNBC and colorectal cancer mouse xenograft models when administered orally at a dose of 100 mg/kg.Formal Name: 6-(4-methyl-1-piperazinyl)-N-(5-methyl-1H-pyrazol-3-yl)-2-[(1E)-2-phenylethenyl]-4-pyrimidinamine, 2R,3R-dihydroxybutanedioate. CAS Number: 1453868-32-0. Molecular Formula: C21H25N7 . C4H6O6. Formula Weight: 525.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMSO: 20 mg/ml, DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml, Ethanol: 5 mg/ml. lambdamax: 203, 269 nm. SMILES: CN(CC1)CCN1C2=CC(NC3=NNC(C)=C3)=NC(/C=C/C4=CC=CC=C4)=N2.OC([C@H](O)[C@@H](O)C(O)=O)=O. InChi Code: InChI=1S/C21H25N7.C4H6O6/c1-16-14-20(26-25-16)23-19-15-21(28-12-10-27(2)11-13-28)24-18(22-19)9-8-17-6-4-3-5-7-17,5-1(3(7)8)2(6)4(9)10/h3-9,14-15H,10-13H2,1-2H3,(H2,22,23,24,25,26),1-2,5-6H,(H,7,8)(H,9,10)/b9-8+,/t,1-,2-/m.1/s1. InChi Key: KGWWHPZQLVVAPT-STTJLUEPSA-N.