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| | CEP-32496 (free base) Basic information |
| Product Name: | CEP-32496 (free base) | | Synonyms: | CEP-32496 (free base);1-[3-[(6,7-Dimethoxyquinazolin-4-yl)oxy]phenyl]-3-[5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl]urea;Urea, N-[3-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl]-N-[5-(2,2,2-trifluoro-1,1-dimethylethyl)-3-isoxazolyl]-;AC 013773;AC013773;AC-013773. Agerafenib;CEP-32496 FREE BASE;AC013773; AC 013773; AC-013773. AGERAFENIB;1-[3-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-[5-(1,1,1-trifluoro-2-methylpropan-2-yl)-1,2-oxazol-3-yl]urea | | CAS: | 1188910-76-0 | | MF: | C24H22F3N5O5 | | MW: | 517.46 | | EINECS: | | | Product Categories: | Inhibitors;MAPK | | Mol File: | 1188910-76-0.mol |  |
| | CEP-32496 (free base) Chemical Properties |
| storage temp. | Store at -20°C | | solubility | ≥25.85 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH | | form | A crystalline solid | | CAS DataBase Reference | 1188910-76-0 |
| | CEP-32496 (free base) Usage And Synthesis |
| Description | 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. | | Uses | CEP 32496 is an orally active BRAFV600E inhibitor with selective cellular and in vivo antitumor activity. | | references | [1] rowbottom mw1, faraoni r, chao q, campbell bt, lai ag, setti e, ezawa m, sprankle kg, abraham s, tran l, struss b, gibney m, armstrong rc,gunawardane rn, nepomuceno rr, valenta i, hua h, gardner mf, cramer md, gitnick d, insko de, apuy jl, jones-bolin s, ghose ak, herbertz t, ator ma,dorsey bd, ruggeri b, williams m, bhagwat s, james j, holladay mw. identification of 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2 -methylpropan- 2-yl) isoxazol-3-yl) urea hydrochloride (cep-32496), a highly potent and orally efficacious inhibitor of v-raf murine sarcoma viral oncogene homologue b1 (braf) v600e. j med chem. 2012 feb 9;55(3):1082-105. doi: 10.1021/jm2009925. epub 2012 jan 23. |
| | CEP-32496 (free base) Preparation Products And Raw materials |
| Raw materials | [5-(2,2,2-TRIFLUORO-1,1-DIMETHYL-ETHYL)-ISOXAZOL-3-YL]-CARBAMIC ACID PHENYL ESTER-->5-(1,1,1-Trifluoro-2-methylpropan-2-yl)isoxazol-3-amine-->methyl 3,3,3-trifluoro-2,2-dimethylpropanoate-->1188911-73-0-->3,3,3-TRIFLUORO-2,2-DIMETHYLPROPIONIC A&-->3-[(6,7-dimethoxy-4-quinazolinyl)oxy]aniline-->4-Chloro-6,7-dimethoxyquinazoline-->3-Aminophenol |
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