1188910-76-0 Usage
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.
Check Digit Verification of cas no
The CAS Registry Mumber 1188910-76-0 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,1,8,8,9,1 and 0 respectively; the second part has 2 digits, 7 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 1188910-76:
(9*1)+(8*1)+(7*8)+(6*8)+(5*9)+(4*1)+(3*0)+(2*7)+(1*6)=190
190 % 10 = 0
So 1188910-76-0 is a valid CAS Registry Number.
1188910-76-0Relevant articles and documents
SOLID STATE FORMS OF A QUINAZOLINE DERIVATIVE AND ITS USE AS A BRAF INHIBITOR
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Paragraph 23, (2014/10/18)
This application relates to various salts and solid state forms of Compound (I). The application also relates to pharmaceutical compositions and therapeutic uses of these materials and compositions.
