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VER 155008

现货
Catalog No.
A4387
HSP 70抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 850.00
现货
10mg
¥ 750.00
现货
50mg
¥ 2,850.00
现货

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Background

VER 155008 is a potent inhibitor of heat shock protein 70 (Hsp70) family of chaperones, which have been shown to contribute to cancer cell survival via anti-apoptotic functions, that inhibits Hsp70 (with the value of 50% inhibition concentration IC50 of 0.5 μM) as well as heat shock cognate 71 kDa protein (Hsc70) and 78 kDa glucose-regulated protein (Grp78) but to a lesser extent. X-ray crystallography analysis reveals that VER 155008 binds to the ATPase pocket of Hsp70 leading to the inhibition of the intrinsic ATPase activity of Hsp70. Study results also have demonstrated that VER 155008 induces cell proliferation and apoptosis in human cancer cell lines.

Reference

Massey AJ, Williamson DS, Browne H, Murray JB, Dokurno P, Shaw T, Macias AT, Daniels Z, Geoffroy S, Dopson M, Lavan P, Matassova N, Francis GL, Graham CJ, Parsons R, Wang Y, Padfield A, Comer M, Drysdale MJ, Wood M. A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemother Pharmacol. 2010; 66(3): 535-545

文献引用

1.He XM, Liu L, Cheng TY. "HSC70 from Haemaphysalis flava (Acari: Ixodidae) exerts anticoagulation activity in vitro." Ticks Tick Borne Dis. 2018 Oct 17. pii: S1877-959X(18)30258-9. PMID:30366643
2.Santarriaga S, Haver HN, et al. "SRCP1 Conveys Resistance to Polyglutamine Aggregation." Mol Cell. 2018 Jul 19;71(2):216-228.e7. PMID:30029002
3.XiChuan Tanga, LiWei Tanb, et al. "Gold nanorods together with HSP inhibitor-VER-155008 micelles for colon cancer mild-temperature photothermal therapy." Acta Pharmaceutica Sinica B Available online 5 June 2018.
4.Tang, Pei-Ciao, and Glen M. Watson. "Proteomic identification of hair cell repair proteins in the model sea anemone Nematostella vectensis." Hearing research (2015). PMID:26183436

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt556.4
Cas No.1134156-31-2
FormulaC25H23Cl2N7O4
Synonymsadenosine-derived inhibitor, VER155008, VER-155008
Solubility≥27.8mg/mL in DMSO, ≥4.65 mg/mL in EtOH with ultrasonic and warming, <2.25 mg/mL in H2O
Chemical Name4-[[(2R,3S,4R,5R)-5-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethyl]benzonitrile
SDFDownload SDF
Canonical SMILESC1=CC(=CC=C1COCC2C(C(C(O2)N3C4=C(C(=NC=N4)N)N=C3NCC5=CC(=C(C=C5)Cl)Cl)O)O)C#N
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。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。

试验操作

激酶实验 [1,2]:

Hsc70、Hsp70和Grp78荧光偏振 (FP) 试验

在100 mM Tris pH 7.4,150 mM KCl和5 mM CaCl2的100 uL缓冲溶液中进行Hsp70的FP试验。采用96孔黑色聚苯乙烯板(具有高结合表面)和Fusion酶标仪进行试验。N6-(6-amino)hexyl-ATP-5-FAM与GST-HSP70 3-382自身蛋白质制剂在试验缓冲液中的最终浓度分别为20 nM和400 nM。使用最终浓度为5%的DMSO测定化合物的10倍IC50值。在读取Fusion(激发波长:485 nm,发射波长:535 nm)数据之前,将试验混合物孵育3小时。使用XLFit 4,对4组参数进行回归分析。按上述方法,使用相同的N6-(6-amino)hexyl-ATP-5-FAM作为FP探针,开展Hsc70和Grp78的FP试验。对于Hsc70,蛋白质和探针浓度分别为0.3 μM和20 nM,将其置于22 ℃下孵育30分钟。对于Grp78,蛋白质和探针浓度分别为2 μM和10 nM,将其置于22 ℃下孵育2小时。对于Hsc70和Grp78,FAM-ATP探针的KD值分别为0.24 μM和2 μM。

细胞实验 [1]:

细胞系

BT474、MB-468、HCT116和HT29细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C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 °C可放置数月。

反应条件

50 μM;72小时

实验结果

在人类乳腺癌和结肠癌细胞系BT474、MB-468、HCT116和HT29中,VER 155008抑制细胞增殖,其GI50值为5.3 ~ 14.4 μM。此外,在HCT116和BT474细胞中,VER 155008诱导Hsp90目标蛋白降解。

动物实验 [1]:

动物模型

携带HCT116肿瘤的小鼠模型

给药剂量

25或40 mg/kg;静脉注射

实验结果

在携带HCT116肿瘤的小鼠模型中,VER 155008被快速代谢和清除。同时,VER 155008将肿瘤水平降至可预测的药理活性水平以下。

其它注意事项

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]. Massey AJ, Williamson DS, Browne H, Murray JB, Dokurno P, Shaw T, Macias AT, Daniels Z, Geoffroy S, Dopson M, Lavan P, Matassova N, Francis GL, Graham CJ, Parsons R, Wang Y, Padfield A, Comer M, Drysdale MJ, Wood M. A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemother Pharmacol. 2010; 66(3): 535-545

[2]. Williamson DS, Borgognoni J, Clay A, Daniels Z, Dokurno P, Drysdale MJ, Foloppe N, Francis GL, Graham CJ, Howes R, Macias AT, Murray JB, Parsons R, Shaw T, Surgenor AE, Terry L, Wang Y, Wood M, Massey AJ. Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design. J Med Chem. 2009 Mar 26;52(6):1510-3.

生物活性

描述 VER 155008是一种新型的腺苷衍生的热休克蛋白70(HSP 70)的抑制剂,IC50值为0.5 μM。
靶点 HSP 70          
IC50 0.5 μM          

质量控制

化学结构

VER 155008

相关生物数据

VER 155008

相关生物数据

VER 155008

相关生物数据

VER 155008