AZ304

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AZ304 是一种新型强效双 BRAF 抑制剂，针对野生型 BRAF、V600E 突变体 BRAF 和野生型 CRAF 的激酶结构域，IC50 分别为 79 nM、38 nM 和 68 nM。

AZ304 is a novel potent, dual BRAF inhibitor targeting the kinase domains of wild type BRAF, V600E mutant BRAF and wild type CRAF with IC50 of 79 nM, 38 nM and 68 nM, respectively; also potentlt inhibits p38 and CSF1R with IC50 of 6 and 35 nM, has no activity for MAP3K7, CSK, IGF1R, EGFR, FGFR, CDK2, CDK4, JAK2, SRC (IC50>5 uM); potently reduces p-ERK with mean EC50 of 65 nM in the V600E mutant BRAF containing melanoma cell line A375, EC50 of 60 nM in wild type BRAF melanoma cell line SK-MEL-31; inhibits cell proliferation in mutant BRAF, wt BRAF/RAS and mutant RAS with IC50 of 0.08-7.72 uM, 0.43-11.7 uM 0.9-16.66 uM, respectively; Cetuximab enhances the potency of AZ304 independently of BRAF mutational status in vivo.

AZ304 (1 nM-100 μM) potently reduces ERK phosphorylation (p-ERK), with a mean EC50 of 65 nM in the V600E mutant BRAF containing melanoma cell line A375, and EC50s of 52 nM, 60 nM in the wild type BRAF melanoma cell line SK-MEL-31 with and without EGF.AZ304 also potently inhibits p-p38 in both BRAF genetic statuses cell lines.AZ304 (0, 0.1, 1, 10, 100 μM, 48 and 72 hours) dose-dependently inhibits the growth of RKO, HT-29, DiFi, and Caco-2, with GI50s of 4.539 μM, 3.896 μM, 4.987 μM, 1.763 μM (48 hours) and 0.5032 μM, 0.3887 μM, 0.6354 μM, 0.3772 μM (72 hours), respectively.AZ304 (2 μM, 36 and 48 hours) decreases BRAF, p-ERK, p-AKT and p-mTOR levels, increases p-EGFR in both BRAF V600E mutant and BRAF wild type cells. AZ304 down-regulates p-EGFR, inhibits p-ERK, more potently suppresses BRAF, ERK, AKT and mTOR signalling pathways in combination with C225. Cell Proliferation Assay Cell Line:RKO, HT-29, DiFi, Caco-2 cells Concentration:0, 0.1, 1, 10, 100 μM Incubation Time:48, 72 hours Result:Dose-dependently inhibited the growth of V600E mutant BRAF cell lines (RKO, HT-29) and wild-type BRAF cell lines (DiFi, Caco-2).

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AZ 304 | AZ-304

MAPK/ERK Signaling

Raf

B-RAFV600E|B-RAF|C-RAF|p38|CSF1R

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942507-42-8

451.53

C27H25N5O2

>98% (HPLC)

DMSO: 85 mg/mL; Ethanol: 4 mg/mL; Water: Insoluble （ < 1 mg/ml refers to the product slightly soluble or insoluble )

O=C(NC1=CC=C(C)C(NC2=C3C=CC(OC)=CC3=NC=N2)=C1)C4=CC=CC(C(C)(C#N)C)=C4

3-(2-cyanopropan-2-yl)-N-(3-((7-methoxyquinazolin-4-yl)amino)-4-methylphenyl)benzamide

(-20℃)

With Ice Pack

≥ 2 years