"目录号: HY-15199
MAPK/ERK Pathway-
CEP-32496盐酸盐是BRAF（V600E/WT）和c-Raf抑制剂，Kd分别为14 nM/36 nM和39 nM，同时还能抑制Abl-1，c-Kit，Ret，PDGFRβ和VEGFR2，对MEK-1，MEK-2，ERK-1和ERK-2无明显亲和力。
Raf
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生物活性
Description
CEP-32496 Hcl is a highly potent inhibitor of BRAF(V600E/WT) and c-Raf with Kd of 14 nM/36 nM and 39 nM, also potent to Abl-1, c-Kit, Ret, PDGFRβ and VEGFR2, respectively; insignificant affinity for MEK-1, MEK-2, ERK-1 and ERK-2. IC50 value: 14 nM/36 nM(Kd,BRAF(V600E/WT) ); 39 nM (Kd,C-Raf) Target: B-Raf/C-RafCEP-32496 is a potent BRAF inhibitor in an in vitro binding assay for mutated BRAF(V600E) (K(d) BRAF(V600E) = 14 nM) and in a mitogen-activated protein (MAP)/extracellular signal-regulated (ER) kinase (MEK) phosphorylation (pMEK) inhibition assay in human melanoma (A375) and colorectal cancer (Colo-205) cell lines (IC(50) = 78 and 60 nmol/L). In vitro, CEP-32496 has multikinase binding activity at other cancer targets of interest; however, it exhibits selective cellular cytotoxicity for BRAF(V600E) versus wild-type cells.
Clinical Trial
NCT01877811
Ignyta, Inc.
Solid Tumors
June 2013
Phase 1
NCT03052569
Ignyta, Inc.
Cancers With RET Alterations
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References
[1].James J, Ruggeri B, Armstrong RC, et al. CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity. Mol Cancer Ther. 2012 Apr;11(4):930-41.
[2].Rowbottom MW, Faraoni R, Chao Q, et al. 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.