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Xevinapant

Xevinapant

产品编号 T6763   CAS 1071992-99-8
别名: ARRY-334543, SM-406, AT406, Debio-1143

Xevinapant (Debio-1143) 是一种有效的 Smac 模拟物和 IAP 的拮抗剂,能够抑制 XIAP,cIAP1 和 cIAP2 蛋白,Ki 值分别为 66.4,1.9 和 5.1 nM。

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Xevinapant Chemical Structure
Xevinapant, CAS 1071992-99-8
规格 价格/CNY 货期 数量
1 mg ¥ 375 现货
2 mg ¥ 523 现货
5 mg ¥ 828 现货
10 mg ¥ 1,320 现货
25 mg ¥ 2,890 现货
50 mg ¥ 4,370 现货
100 mg ¥ 6,230 现货
200 mg ¥ 8,560 现货
500 mg ¥ 12,700 现货
1 mL * 10 mM (in DMSO) ¥ 1,330 现货
其他形式的 Xevinapant:
产品目录号及名称: Xevinapant (T6763)
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选择批次  
纯度: 99.77%
纯度: 99.48%
纯度: 99.44%
纯度: 99.19%
纯度: 98%
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生物活性
化学信息
存储 & 溶解度
参考文献
产品描述 Xevinapant (Debio-1143) is a potent Smac mimetic and an antagonist of IAP (inhibitor of apoptosis protein via E3 ubiquitin ligase), binding to XIAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 66.4 nM, 1.9 nM, and 5.1 nM, 50- to 100-fold higher affinities than the Smac AVPI peptide. Phase 1.
靶点活性 CIAP2-BIR3:5.1 nM(Ki), XIAP BIR3:66.4 nM(Ki), CIAP1-BIR3:1.9 nM(Ki)
体外活性 AT-406 is a Smac mimetic and appears to mimic closely the AVPI peptide in both hydrogen bonding and hydrophobic interactions with XIAP, with additional hydrophobic contacts with W323 of XIAP. AT-406 is more sensitive to these IAPs than Smac AVPI peptide with 50-100 fold binding affinities. AT-406 (at 1 μM) completely restores the activity of caspase-9, which is suppressed by 500 nM XIAP BIR3 in a cell-free system. In MDA-MB-231 cell, AT-406 induces rapid cellular cIAP1 degradation and also pulls down the cellular XIAP protein. AT-406 effectively inhibits lots of human cancer cell lines and shows IC50 of 144 and 142 nM in MDA-MB-231 cell and SK-OV-3 ovarian cell, with low toxicity against normal-like human breast epithelial MCF-12F cells and primary human normal prostate epithelial cells. AT-406 induces apoptosis in MDA-MB-231 cell by inducing activation of caspase-3 and cleavage of PARP. [1]
体内活性 AT-406 has good pharmacokinetic (PK) properties and oral bioavailability in mice, rats, non-human primates, and dogs. In the MDA-MB-231 xenograft, AT-406 effectively induces cIAP1 degradation and processing of procaspase-8, cleavage of PARP in tumor tissues at 100 mg/kg with well toleration even at 200 mg/kg. AT-406 induces significant tumor growth inhibition with p of 0.0012 at 100 mg/kg. [1]
激酶实验 Fluorescence Polarization Based Assays for XIAP, cIAP1, and cIAP2 BIR3 Proteins: FL-AT-406 (the fluorescently tagged AT-406) is employed to develop a set of new FP assays for determination of the binding affinities of Smac mimetics to XIAP, cIAP-1, and cIAP-2 BIR3 proteins. The Kd value of FL-AT-406 to each IAP protein is determined by titration experiments using a fixed concentration of FL-AT-406 and different concentrations of the protein up to full saturation. Fluorescence polarization values are measured using an Infinite M-1000 plate reader in Microfluor 2 96-well, black, round-bottom plates. To each well, FL-AT-406 (2, 1, and 1 nM for experiments with XIAP BIR3, cIAP-1 BIR3, and cIAP-2 BIR3, respectively) and different concentrations of the protein are added to a final volume of 125 μL in the assay buffer (100 mM potassium phosphate, pH 7.5, 100 μg/mL bovine γ-globulin, 0.02% sodium azide, with 4% DMSO). Plates are mixed and incubated at room temperature for 2-3 hours with gentle shaking. The polarization values in millipolarization units (mP) are measured at an excitation wavelength of 485 nm and an emission wavelength of 530 nm. Equilibrium dissociation constants (Kd) are then calculated by fitting the sigmoidal dose-dependent FP increases as a function of protein concentrations using Graphpad Prism 5.0 software. In competitive binding experiments for XIAP3 BIR3, AT-406 is incubated with 20 nM XIAP BIR3 protein and 2 nM FL-AT-406 in the assay buffer (100 mM potassium phosphate, pH 7.5; 100 μg/mL bovine γ-globulin; 0.02% sodium azide). In competitive binding experiments for cIAP1 BIR3 protein, 3 nM protein and 1 nM FL-AT-406 are used. In competitive binding experiments for cIAP2 BIR3, 5 nM protein and 1 nM FL-AT-406 are used. For each competitive binding experiment, polarization values are measured after 2-3 hours of incubation using an Infinite M-1000 plate reader.The IC50 value, the inhibitor concentration at which 50% of the bound tracer is displaced, is determined from the plot using nonlinear least-squares analysis. Curve fitting is performed using the PRISM software. A Ki value for AT-406 is calculated.
细胞实验 Cells are seeded in 96-well flat bottom cell culture plates at a density of (3-4) × 103 cells/well with AT-406 and incubated for 4 days. The rate of cell growth inhibition after treatment with different concentrations of AT-406 is determined by assaying with (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt (WST-8). WST-8 is added to each well to a final concentration of 10%, and then the plates are incubated at 37 °C for 2−3 hours. The absorbance of the samples is measured at 450 nm using a TECAN ULTRA reader. Concentration of AT-406 that inhibited cell growth by 50% (IC50) is calculated by comparing absorbance in the untreated cells and the cells treated with AT-406. (Only for Reference)
别名 ARRY-334543, SM-406, AT406, Debio-1143
分子量 561.71
分子式 C32H43N5O4
CAS No. 1071992-99-8

存储

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度

H2O: < 1 mg/mL (insoluble or slightly soluble)

DMSO: 93 mg/mL (165.6 mM)

Ethanol: 93 mg/mL (165.6 mM)

溶液配制表

可选溶剂 浓度 体积 质量 1 mg 5 mg 10 mg 25 mg
DMSO / Ethanol 1 mM 1.7803 mL 8.9014 mL 17.8028 mL 44.507 mL
5 mM 0.3561 mL 1.7803 mL 3.5606 mL 8.9014 mL
10 mM 0.178 mL 0.8901 mL 1.7803 mL 4.4507 mL
20 mM 0.089 mL 0.4451 mL 0.8901 mL 2.2253 mL
50 mM 0.0356 mL 0.178 mL 0.3561 mL 0.8901 mL
100 mM 0.0178 mL 0.089 mL 0.178 mL 0.4451 mL

计算器

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分子量计算器
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参考文献

1. Cai Q, et al. J Med Chem, 2011, 54(8), 2714-2726.
Polygalacin D LCL161 Embelin Phenoxodiol ASTX660 GDC-0152 AZD5582 SM-164 Hydrochloride (957135-43-2 free base)

相关化合物库

该产品包含在如下化合物库中:
抗癌活性化合物库 抗癌临床化合物库 抗癌药物库 HIF-1化合物库 药物功能重定位化合物库 细胞凋亡化合物库 经典已知活性库 PPI抑制剂库 铜死亡化合物库 泛素化化合物库

剂量换算

对于不同动物的给药剂量换算,您也可以参考 更多...

体内实验配液计算器

请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。

母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。

体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。

第一步:请输入动物实验的基本信息
剂量
mg/kg
每只动物体重
g
给药体积
μL
动物数量
第二步:请输入动物体内配方组成,不同的产品配方组成不同,如有配方需求,可先联系我们提供正确的体内配方。
% DMSO
%
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% ddH2O
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技术支持

您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。

Keywords

Xevinapant 1071992-99-8 Apoptosis IAP AT 406 SM 406 ARRY-334543 oral inhibit SM-406 Debio 1143 ovarian degradation Smac ARRY 334543 Inhibitor cancer SM406 AT406 AT-406 mimetic Debio-1143 Debio1143 ARRY334543 inhibitor

 

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