AZ-31

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

一种有效的、高选择性的、口服活性的 ATM 抑制剂，酶 IC50 为 <1.2 nM，细胞 IC50 为 46 nM。

A potent, highly selective and orally active ATM inhibitor with enzyme IC50 of <1.2 nM, cell IC50 of 46 nM; displays excellent selectivity against a panel of kinases including ATR, DNAPK, mTOR, PI3Kα, PI3Kβ, PI3Kγ, GSK3β and KDR; reduces upregulation of p21 and blocks G1 arrest in wild-type but not Cdkn1a(p21CIP/WAF1)-/- mice; showes significant tumor growth reduction in the SW620 xenograft model combined with irinotecan.

AZ31 (0.3-3 μM; 1 h) affects phosphorylation of a panel of ATM targets.AZ31 (10 μM; 1 h) affects stabilization of p53 in H2228 lung cancer cells after radiation. Western Blot AnalysisCell Line:Human glioma cell line Concentration:0.3, 1 and 3 μM Incubation Time:1 hour Result:Blocked phosphorylation of p53-S15, KAP1-S824, and ATM auto-phosphorylation at S1981.Western Blot Analysis Cell Line:H460 and mutant p53 H2228 cell lines Concentration:10 μM Incubation Time:1 hour Result:Destabilized p53 of mutant p53 but not wild-type after radiation.

AZ31 (50-100 mg/kg; p.o. twice a day) shows low brain coverage. Animal Model:Nude miceDosage:50 and 100 mg/kg Administration:Oral gavage; 50 and 100 mg/kg twice a day Result:Exhibited exposure over IC50 at 0.046 μM in brain only for 2-3 hours.

AZ 31 | AZ31

Cell Cycle/DNA Damage

ATM/ATR

ATM/ATR

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2088113-98-6

420.513

C24H28N4O3

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (237.81 mM)

NC(C1=C(N[C@H](C2CCOCC2)C)C3=CC(C4=CN=C(COC)C=C4)=CC=C3N=C1)=O

(S)-6-(6-(methoxymethyl)pyridin-3-yl)-4-((1-(tetrahydro-2H-pyran-4-yl)ethyl)amino)quinoline-3-carboxamide

(-20℃)

With Ice Pack

≥ 2 years