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AZD 7762 hydrochloride

Names

[ CAS No. ]:
1246094-78-9

[ Name ]:
AZD 7762 hydrochloride

[Synonym ]:
AZD7762 hydrochloride

Biological Activity

[Description]:

AZD-7762 hydrochloride is a potent ATP-competitive checkpoint kinase (Chk) inhibitor in with an IC50 of 5 nM for Chk1.

[Related Catalog]:

Research Areas >> Cancer
Signaling Pathways >> Cell Cycle/DNA Damage >> Checkpoint Kinase (Chk)

[Target]

Chk1:5 nM (IC50)

Chk2:5 nM (IC50)


[In Vitro]

AZD-7762 hydrochloride 在体外是一种同样有效的 Chk1 和 Chk2 抑制剂。AZD-7762 hydrochloride 有效抑制 Chk1 和 Chk2，消除 DNA 损伤诱导的 S 和 G2 检查点，增强 NSC 613327 和 SKF 104864A 的功效，并调节下游检查点通路蛋白。AZD-7762 hydrochloride 有效抑制 cdc25C 肽的 Chk1 磷酸化，通过闪烁亲近测定法测量，IC50 为 5 nM。AZD-7762 hydrochloride 的 Ki 确定为 3.6 nM。动力学表征表明 AZD-7762 hydrochloride 结合在 Chk1 的 ATP 结合位点，并被认为以可逆方式直接竞争 ATP 结合。AZD-7762 hydrochloride 显示可消除喜树碱诱导的 G2 阻滞，平均 EC50 为 10 nM (n=12)，最大消除范围为 100 nM[1]。

[In Vivo]

在大鼠 H460-DNp53 异种移植研究中，AZD-7762 hydrochloride（10 mg/kg 和 20 mg/kg）以剂量依赖性方式增强 NSC 613327 的抗肿瘤活性。即随着剂量增加，抑制率 (%T/C) 分别降低至 48% 和 32%。在与 CPT-11 联合的小鼠异种移植研究中，AZD-7762 hydrochloride 与 CPT-11 联合处理，可显著增加 CPT-11 活性，%T/C 分别显着增加至 -66% 和 -67%[1]。AZD7762 hydrochloride 与 CX-5461 联合使用，在体外和体内诱导 Tp53-null (Tp53-/-) Eμ-Myc 淋巴瘤细胞死亡[2]。

[References]

[1]. Zabludoff SD, et al. AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol Cancer Ther. 2008 Sep;7(9):2955-66.  

[2]. Quin J, et al. Inhibition of RNA polymerase I transcription initiation by CX-5461 activates non-canonical ATM/ATR signaling. Oncotarget. 2016 Aug 2;7(31):49800-49818.  

Chemical & Physical Properties

[ Molecular Formula ]:
C17H20ClFN4O2S

[ Molecular Weight ]:
398.88

[ Exact Mass ]:
398.09800

[ PSA ]:
124.49000

[ LogP ]:
4.82160

[ Storage condition ]:
-20°C

Safety Information

[ Symbol ]:

GHS05, GHS07

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H302-H318

[ Precautionary Statements ]:
P280-P305 + P351 + P338

[ RIDADR ]:
NONH for all modes of transport

Related Compounds