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AZD5582

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Chemical Structure| 1258392-53-8 同义名 : -
CAS号 : 1258392-53-8
货号 : A961946
分子式 : C58H78N8O8
纯度 : 99%+
分子量 : 1015.289
MDL号 : MFCD28411397
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(103.42 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • cIAP

    cIAP1, IC50:15 nM

    cIAP2, IC50:21 nM

  • XIAP

    XIAP, IC50:15 nM
描述 AZD5582 is an IAP inhibitor with IC50 values of 15nM, 21nM and 15nM for cIAP1, cIAP2 and XIAP (measured by fluoresence polarization assays), respectively. Treatment with AZD5582 caused cIAP1 degradation with IC50 of 0.1nM and cell growth inhibition with GI50<0.06nM in MDA-MB-231 cells. And induction of cell apoptosis could be observed by AZD5582 at subnanomolar concentration. A single intravenous dose of AZD5582 caused dose (0.05-3mg/kg)- and time (4, 6 and 18h)-degradation of cIAP1 and increased cleaved caspase3 in mice bearing MDA-MB-231 xenografts, suggesting the pharmacodynamics of this compound in vivo. Intravenous injection with AZD5582 at dose of 0.1, 0.5 and 3mg/kg, once a week for 2 weeks, dose-dependently inhibited growth inhibition in the MDA-MB-231 xenograft efficacy model[1]. AZD5582 can target cIAP1 to induce TNF-α-induced apoptosis accompanied with a decrease of Mcl-1 protein, a member of the Bcl-2 family, but not that of Bcl-2 and Bcl-xL[2].
作用机制 AZD5582 can bind potently to the BIR3 domains of cIAP1, cIAP2 and XIAP and cause cIAP1 degradation.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
BT549 cells Growth inhibition assay Growth inhibition of human BT549 cells 24320998
MDA-MB-231 cells Growth inhibition assay 48 h Antiproliferative activity against human MDA-MB-231 cells assessed as growth inhibition after 48 hrs by Alamar Blue assay, GI50=6e-05 μM 24320998
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

0.98mL

0.20mL

0.10mL

4.92mL

0.98mL

0.49mL

9.85mL

1.97mL

0.98mL
参考文献

[1]Hennessy EJ, Adam A, et al. Discovery of a novel class of dimeric Smac mimetics as potent IAP antagonists resulting in a clinical candidate for the treatment of cancer (AZD5582). J Med Chem. 2013 Dec 27;56(24):9897-919.

[2]Moon JH, Shin JS, et al. A novel small-molecule IAP antagonist, AZD5582, draws Mcl-1 down-regulation for induction of apoptosis through targeting of cIAP1 and XIAP in human pancreatic cancer. Oncotarget. 2015 Sep 29;6(29):26895-908.