CEP-40783

CEP-40783 is an inhibitor of the receptor tyrosine kinases Axl and c-MET (IC50s = 7 and 12 nM, respectively). It inhibits Axl in 293GT cells expressing Axl and c-MET in NCI H1299 non-small cell lung cancer (NSCLC) cells with IC50 values of 0.26 and 6 nM, respectively. It also inhibits the receptor tyrosine kinases TYRO3 and MER (IC50s = 3.5 and 1.89 nM, respectively). CEP-40783 (0.3 mg/kg) induces complete regression of tumors in an Axl/NIH3T3 mouse xenograft model and reduces the metastatic tumor burden in mouse orthotopic breast cancer models. It also induces tumor stasis and regression in an EBC-1 NSCLC mouse xenograft model when administered at doses of 3 and 10 mg/kg, respectively. CEP-40783 reduces tumor growth in an MC38 mouse syngeneic model concomitantly with an increase in leukocyte infiltration into tumors, the production of IFN-gamma in natural killer cells, and the percentage of CD8+ T cells in tumor tissue.Formal Name: N-[4-[(6,7-dimethoxy-4-quinolinyl)oxy]-3-fluorophenyl]-3-(4-fluorophenyl)-1,2,3,4-tetrahydro-1-(1-methylethyl)-2,4-dioxo-5-pyrimidinecarboxamide. CAS Number: 1437321-24-8. Synonyms: RXDX-106. Molecular Formula: C31H26F2N4O6. Formula Weight: 588.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMF:PBS (pH 7.2) (1:2): 0.3 mg/ml, DMSO: 5 mg/ml, Ethanol: 2 mg/ml. lambdamax: 232, 240, 299 nm. SMILES: COC(C(OC)=C1)=CC2=C1C(OC3=C(F)C=C(NC(C4=CN(C(C)C)C(N(C5=CC=C(F)C=C5)C4=O)=O)=O)C=C3)=CC=N2. InChi Code: InChI=1S/C31H26F2N4O6/c1-17(2)36-16-22(30(39)37(31(36)40)20-8-5-18(32)6-9-20)29(38)35-19-7-10-26(23(33)13-19)43-25-11-12-34-24-15-28(42-4)27(41-3)14-21(24)25/h5-17H,1-4H3,(H,35,38). InChi Key: FKCWHHYUMFGOPY-UHFFFAOYSA-N.