SM-164

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

SM-164  纯度: 99.65%

SM-164 是一种可渗透细胞的 Smac 类似物。SM-164 与含有 BIR2 和 BIR3 结构域的 XIAP 蛋白结合,IC50 值为 1.39 nM,SM-164 用作 XIAP 的强效拮抗剂。

SM-164

SM-164 Chemical Structure

CAS No. : 957135-43-2

规格 价格 是否有货 数量
2 mg ¥2170 In-stock
5 mg ¥3255 In-stock
10 mg ¥5000 In-stock
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SM-164 相关产品

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生物活性

SM-164 is a cell-permeable Smac mimetic compound. SM-164 binds to XIAP protein containing both the BIR2 and BIR3 domains with an IC50 value of 1.39 nM and functions as an extremely potent antagonist of XIAP.

IC50 & Target[1][2]

cIAP-1

0.31 nM (Ki)

cIAP-2

1.1 nM (Ki)

cIAP

 

体外研究
(In Vitro)

SM-164 is a non-peptide, cell-permeable, bivalent small-molecule, which mimics Smac protein for targeting XIAP. SM-164 binds to XIAP containing both BIR domains with an IC50 value of 1.39 nM, being 300 and 7000-times more potent than its monovalent counterparts and the natural Smac AVPI peptide, respectively. SM-164 concurrently interacts with both BIR domains in XIAP and functions as an ultra-potent antagonist of XIAP in both cell-free functional and cell-based assays. SM-164 targets cellular XIAP and effectively induces apoptosis at concentrations as low as 1 nM in leukemia cancer cells, while having a minimal toxicity to normal human primary cells at 10,000 nM[1]. The binding affinities of SM-164 to XIAP, cIAP-1, and cIAP-2 proteins are determined using fluorescence-polarization based assays. SM-164 has a Ki value of 0.56 nM to XIAP protein containing both BIR2 and BIR3 domains. SM-164 has a Ki value of 0.31 nM to cIAP-1 protein containing both BIR2 and BIR3 domains. SM-164 binds to cIAP-2 BIR3 protein with Ki values of 1.1 nM. Addition of exogenous TNFα can significantly enhance the activity of these Smac mimetics, especially for SM-164, in resistant cancer cell lines such as HCT116 and MDA-MB-453[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

SM-164 is evaluated for its ability to inhibit tumor growth. SM-164 is highly effective in inhibition of tumor growth and capable of achieving tumor regression in the MDA-MB-231 xenograft model. Treatment with SM-164 at 1 mg/kg completely inhibits tumor growth during the treatment. Treatment with SM-164 at 5 mg/kg reduces the tumor volume from 147±54 mm3 at the beginning of the treatment (day 25) to 54±32 mm3 at the end of the treatment (day 36), a reduction of 65%. The strong antitumor activity by SM-164 is long lasting and not transient. SM-164 at 5 mg/kg is statistically more effective than Taxotere at the end of the treatment (P<0.01) or when the tumor size in the control group reached 750 mm3 (P<0.02)[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

分子量

1121.42

Formula

C62H84N14O6

CAS 号

957135-43-2

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 25 mg/mL (22.29 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 0.8917 mL 4.4586 mL 8.9173 mL
5 mM 0.1783 mL 0.8917 mL 1.7835 mL
10 mM 0.0892 mL 0.4459 mL 0.8917 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: 0.83 mg/mL (0.74 mM); Clear solution; Need ultrasonic

    此方案可获得 0.83 mg/mL (0.74 mM) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 8.3 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH₂O 中,得到澄清透明的生理盐水溶液

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
  • [1]. Sun H, et al. Design, synthesis, and characterization of a potent, nonpeptide, cell-permeable, bivalent Smac mimetic that concurrently targets both the BIR2 and BIR3 domains in XIAP. J Am Chem Soc. 2007 Dec 12;129(49):15279-94.

    [2]. Lu J, et al. SM-164: a novel, bivalent Smac mimetic that induces apoptosis and tumor regression by concurrent removal of the blockade of cIAP-1/2 and XIAP. Cancer Res. 2008 Nov 15;68(22):9384-93.

Kinase Assay
[2]

A set of sensitive and quantitative fluorescence polarization (FP)-based assays are developed to determine the binding affinities of our designed Smac mimetics to XIAP BIR3, XIAP containing both BIR2 and BIR3 domains, cIAP-1 BIR3, cIAP-1 containing both BIR2 and BIR3 domains, and cIAP-2 protein. The FP-based assay for XIAP BIR3 protein is measured. Briefly, 5-carboxyfluorescein is coupled to the lysine side chain of a mutated Smac peptide with the sequence (AbuRPFK-Fam) and this fluorescently tagged peptide (named SM5F) is used as the fluorescent tracer in FP-based binding assay to XIAP BIR3. The Kd value of this fluorescent tracer is determined to be 17.9 nM to XIAP BIR3. In competitive binding experiments, a tested compound is incubated with 30 nM of XIAP BIR3 protein and 5 nM of SM5F in the assay buffer (100 mM potassium phosphate, pH 7.5; 100μg/mL bovine gamma globulin; 0.02 % sodium azide)[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[2]

HCT116 colon cancer cells are treated with SM-164 (1, 10, and 100 nM) alone, TNFα alone, or the combination for 48 h. Cell growth inhibition is determined by a WST assay[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

Mice[2]
SCID mice (8-10 per group) bearing MDA-MB-231 xenograft tumors are treated i.v. with 1 and 5 mg/kg of SM-164 or 7.5 mg/kg of Taxotere or vehicle control daily, 5 d/wk for 2 wk. Tumor sizes and animal weights are measured thrice a week[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

参考文献
  • [1]. Sun H, et al. Design, synthesis, and characterization of a potent, nonpeptide, cell-permeable, bivalent Smac mimetic that concurrently targets both the BIR2 and BIR3 domains in XIAP. J Am Chem Soc. 2007 Dec 12;129(49):15279-94.

    [2]. Lu J, et al. SM-164: a novel, bivalent Smac mimetic that induces apoptosis and tumor regression by concurrent removal of the blockade of cIAP-1/2 and XIAP. Cancer Res. 2008 Nov 15;68(22):9384-93.

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