Birinapant (TL32711)
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.
Birinapant (TL32711)是一种有效的XIAP和cIAP1拮抗剂,Kd值分别为45 nM和Kd<1 nM[1]。
Birinapant不仅与cIAP1、cIAP2、XIAP分离的BIR3结构域结合,与ML-IAP的单个BIR结构域也有高亲和性,快速降解结合TRAF2的 cIAP1和cIAP2,从而抑制TNF介导的NF-κB的激活。此外,Birinapant可以促进caspase-8的形成:RIPK1复合体对TNF的刺激作出响应,从而导致下游caspase的激活[4]。
Birinapant具有广泛的IAP拮抗作用。Birinapant可以引起cIAP1的快速降解,PARP的切割,caspase的激活以及抑制NF-κB 的激活。Birinapant与TNF-α联合使用的效果比单独给药效果更好。在体内,Birinapant抑制肿瘤细胞的生长。在一个亲代细胞系中,Birinapant与TNF-α联合使用可以抑制获得耐药性的黑色素瘤细胞的生长[1, 2]。
参考文献:
1. Allensworth JL, Sauer S, Lyerly HK, et al. Smac mimetic Birinapant induces apoptosis and enhances TRAIL potency in inflammatory breast cancer cells in an IAP-dependent and TNF-a-independent mechanism. Breast Cancer Research, 2013, 137:359-371.
2. Krepler C, Chunduru SK, Halloran MB, et al. The novel SMAC mimetic birinapant exhibits potent activity against human melanoma cells. Clinical Cancer Research, 2013, 19 (7): 1784-1794.
3. Nguyen QD, Lavdas I, Gubbins J, et al. Temporal and Spatial Evolution of Therapy-Induced Tumor Apoptosis Detected by Caspase-3–Selective Molecular Imaging. Clinical Cancer Research, 2013, 19 (14): 3914-3924.
4. Benetatos CA, Mitsuuchi Y, Burns JM, et al. Birinapant (TL32711), a Bivalent SMAC Mimetic, Targets TRAF2-Associated cIAPs, Abrogates TNF-Induced NF-kB Activation, and Is Active in Patient-Derived Xenograft Models. 2014, 13(4):867-879.
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Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 806.94 |
Cas No. | 1260251-31-7 |
Formula | C42H56F2N8O6 |
Solubility | ≥40.35 mg/mL in DMSO; insoluble in H2O; ≥46.9 mg/mL in EtOH |
Chemical Name | (2S,2'S)-N,N'-((2S,2'S)-((3S,3'S,5R,5'R)-5,5'-((6,6'-difluoro-1H,1'H-[2,2'-biindole]-3,3'-diyl)bis(methylene))bis(3-hydroxypyrrolidine-5,1-diyl))bis(1-oxobutane-2,1-diyl))bis(2-(methylamino)propanamide) |
SDF | Download SDF |
Canonical SMILES | CCC(C(=O)N1CC(CC1CC2=C(NC3=C2C=CC(=C3)F)C4=C(C5=C(N4)C=C(C=C5)F)CC6CC(CN6C(=O)C(CC)NC(=O)C(C)NC)O)O)NC(=O)C(C)NC |
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。 |
细胞实验 [1]: | |
细胞系 |
SUM149和SUM190炎症性乳腺癌细胞 |
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 |
24 h-96 h |
实验结果 |
Birinapant引起cIAP1和2的明显降解,添加TRAIL不能使其增强。与SUM149中的GT13402相比,Birinapant在增加TRAIL效能方面更有效。此外,Birinapant以剂量依赖性方式显著降低SUM190细胞的活力。 |
动物实验[2]: | |
动物模型 |
黑色素瘤肿瘤异种移植小鼠 |
给药剂量 |
腹腔注射,30 mg/kg |
制备方法 |
溶于12.5%Captisol的蒸馏水溶液中 |
实验结果 |
与对照相比,在Birinapant处理的小鼠中,cIAP1蛋白在3小时后降低至低水平,作用持续24小时。在相同肿瘤的活检中,对活化的caspase-3进行染色,与对照相比,在处理后24小时,Birinapant处理的小鼠中的凋亡细胞有所增加。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
References: 1. Allensworth JL, Sauer SJ, Lyerly HK et al. Smac mimetic Birinapant induces apoptosis and enhances TRAIL potency in inflammatory breast cancer cells in an IAP-dependent and TNF-α-independent mechanism. Breast Cancer Res Treat. 2013 Jan;137(2):359-71. 2. Krepler C, Chunduru SK, Halloran MB et al. The novel SMAC mimetic birinapant exhibits potent activity against human melanoma cells. Clin Cancer Res. 2013 Apr 1;19(7):1784-94. |
描述 | Birinapant是XIAP和cIAP1的拮抗剂,Kd值分别为45 nM和Kd<1 nM。 | |||||
靶点 | XIAP | cIAP1 | ||||
IC50 | 45 nM (Kd) | <1 nM (Kd) |
质量控制和MSDS
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