SM-164
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
SM-164是Smac的二价模拟物,对cIAP-1、cIAP-2和XIAP的抑制常数Ki分别为0.31 nM、1.1 nM和0.56 nM。
SM-164是一种抗癌剂。SM-164通过诱导肿瘤细胞中凋亡蛋白抑制子(cIAP)-1/2的降解,拮抗凋亡蛋白的X连锁抑制子(XIAP),诱导TNFα依赖性的凋亡,从而发挥其抗肿瘤作用。SM-164是一个包含两个SM-122类似物的二价模拟物。SM-164与包含BIR2和BIR3结构域的cIAP-1蛋白、包含BIR3的cIAP-2蛋白以及包含BIR2和BIR3的XIAP蛋白相结合,Ki值分别为0.31 nM、1.1 nM和0.56 nM。在肿瘤细胞中,SM-164显著降低cIAP-1的水平至检测不到的水平(1 nM,60 min),有效拮抗XIAP并增强TNFα的分泌。在MDA-MB-231异种移植模型中,SM-164(5 mg/kg)在一小时的时间内显著减少了cIAP-1的水平,并在3小时时激活caspase-8、caspase-9和caspase-3。
参考文献:
1. Lu J, Bai L, Sun H, 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 research, 2008, 68(22): 9384-9393.
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Storage | Store at -20°C |
M.Wt | 1121.42 |
Cas No. | 957135-43-2 |
Formula | C62H84N14O6 |
Solubility | ≥56.07 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
Chemical Name | (3S,6R,10aR)-6-((S)-2-(methylamino)propanamido)-N-((R)-(1-(4-(4-(4-(4-((S)-((3S,6S,10aS)-6-((S)-2-(methylamino)propanamido)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamido)(phenyl)methyl)-1H-1,2,3-triazol-1-yl)butyl)phenyl)butyl)-1H-1,2,3-triazol-4-yl)( |
SDF | Download SDF |
Canonical SMILES | O=C([C@H]1N(C([C@@H](NC([C@H](C)NC)=O)CCCC2)=O)[C@]2([H])CC1)N[C@H](C3=CN(CCCCC4=CC=C(CCCCN5C=C([C@H](NC([C@@H]6CC[C@](CCCC[C@@H]7NC([C@@H](NC)C)=O)([H])N6C7=O)=O)C8=CC=CC=C8)N=N5)C=C4)N=N3)C9=CC=CC=C9 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
激酶实验[1]: | |
基于荧光偏振的XIAP、cIAP-1和cIAP-2蛋白的结合测定 |
为了测定SM-164与含有BIR2和BIR3结构域的XIAP的结合亲和力,使用二价荧光标记示踪物Smac-1F建立基于FP的竞争性结合实验。二价标记的示踪剂与含有BIR2和BIR3结构域的XIAP的Kd值确定为2.3 nM。在竞争性结合实验中,将测试化合物与3 nM含有BIR2和BIR3结构域(残基120-356)的XIAP蛋白一起温育。 |
细胞实验: [1] | |
细胞系 |
MDA-MB-231乳腺癌细胞 |
制备方法 |
溶解度有限,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。 |
反应条件 |
12 h-48 h |
实验结果 |
在MDA-MB-231、SK-OV-3和MALME-3M细胞中,1 nmol/L SM-164孵育12 h分别诱导32%、33%和37%的细胞凋亡。在抗性癌细胞系中,SM-164引起cIAP-1降解,并有效地拮抗细胞XIAP。此外,在所有敏感的癌细胞系中,3至10 nmol/L SM-164诱导含有或不含TNFα的细胞死亡。 |
动物实验: [1] | |
动物模型 |
MDA-MB-231异种移植肿瘤小鼠模型 |
给药剂量 |
静脉注射,单一剂量的5 mg/kg SM-164。 |
实验结果 |
在3小时时间点,SM-164诱导肿瘤组织中明显的凋亡,在6小时时间点,超过50%的肿瘤细胞为TUNEL阳性。SM-164将肿瘤体积从第25天治疗开始时的147 ± 54 mm3降低至第36天治疗结束时的54 ± 32 mm3,减少65%。SM-164治疗也没有表现出明显的体重减轻或毒性迹象。 |
注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。 |
References: 1. Lu J, Bai L, Sun H, Nikolovska-Coleska Z 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. |
Targets | IAP | |||||
IC50 | 0.56 nM/0.31 nM/1.1 nM |
质量控制和MSDS
- 批次: