CEP-32496

B-Raf is a MAP kinase kinase kinase, which functions downstream of Ras family GTPases to activate MEK1/2 and ERK1/2 signaling. Mutations of B-Raf, particularly at Val600, are common in melanomas and melanocytic nevi. CEP-32496 is a potent inhibitor of B-RafV600E (Kd = 14 nM in an in vitro binding assay). It blocks B-RafV600E-dependent phosphorylation of MEK in human melanoma A375 and colorectal cancer COLO 205 cells (IC50s = 78 and 60 nM, respectively). CEP-32496 binds kinases other than B-Raf but displays selective cytotoxicity for cells expressing B-RafV600E. It displays good oral bioavailability in rats, dogs, and monkeys and has single oral dose pharmacodynamics inhibition of both pMEK and pERK in B-RafV600E colon carcinoma xenografts in nude mice.Formal Name: N-[3-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl]-N'-[5-(2,2,2-trifluoro-1,1-dimethylethyl)-3-isoxazolyl]-urea. CAS Number: 1188910-76-0. Molecular Formula: C24H22F3N5O5. Formula Weight: 517.5. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 10 mg/ml, DMF:PBS(pH7.2) (1:2): 0.3 mg/ml, DMSO: 20 mg/ml, Ethanol: 2 mg/ml. lambdamax: 239, 319 nm. SMILES: COC1=C(OC)C=C(C(OC2=CC=CC(NC(NC3=NOC(C(C)(C)C(F)(F)F)=C3)=O)=C2)=NC=N4)C4=C1. InChi Code: InChI=1S/C24H22F3N5O5/c1-23(2,24(25,26)27)19-11-20(32-37-19)31-22(33)30-13-6-5-7-14(8-13)36-21-15-9-17(34-3)18(35-4)10-16(15)28-12-29-21/h5-12H,1-4H3,(H2,30,31,32,33). InChi Key: DKNUPRMJNUQNHR-UHFFFAOYSA-N.