AZD5582

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 model¹. 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-xL².

溶解方案(细胞实验)

DMSO 中的溶解度 : 100 mg/mL (98.49 mM; 超声助溶; 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)

溶解方案(动物实验)

"方案 一": "请依序添加每种溶剂：10% DMSO 40% PEG300 5% Tween-80 45% SalineSolubility: ≥ 2.5 mg/mL (2.46 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水 定容至 1 mL。生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。"

"方案 二": "请依序添加每种溶剂：10% DMSO 90% (20% SBE-β-CD in Saline)Solubility: ≥ 2.5 mg/mL (2.46 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液 中，混合均匀。2 g SBE-β-CD（磺丁基醚 β-环糊精）粉末定容于 10 mL 的生理盐水中，完全溶解至澄清透明。"

"方案 三": "请依序添加每种溶剂：10% DMSO 90% Corn OilSolubility: ≥ 2.5 mg/mL (2.46 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液，此方案实验周期在半个月以上的动物实验酌情使用。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。"

"方案 一": "请依序添加每种溶剂：50% PEG300 50% SalineSolubility: 50 mg/mL (49.25 mM); 澄清溶液; 超声助溶"