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XL-888

现货
Catalog No.
A4388
Hsp90抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 3,200.00
Ship with 10-15 days
5mg
¥ 1,600.00
Ship with 10-15 days
10mg
¥ 2,500.00
Ship with 10-15 days
25mg
¥ 4,400.00
Ship with 10-15 days
50mg
¥ 7,500.00
Ship with 10-15 days

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Background

XL-888 is a novel and orally-bioavailable inhibitor of heat shock protein 90 (HSP90) that selectively inhibits HSP90α and HSP90β with values of 50% inhibition concentration IC50 of 22 nM and 44 nM respectively. It also exerts considerably weaker inhibition against a range of other diverse kinases with IC50 more than 3600 nM for all. X-ray crystallographic analysis reveals that the XL-888 binds to HSP90 through the formation of H-bonding between the N-(R)-sec-butylanthranilamide moiety of XL-888 and ASP93 of HSP90. In recent studies, XL-888 has exhibits strong anti-proliferative activities in a panel of tumor cells with values of IC50 ranging from 0.1 nM to 45.5 nM.

Reference

Paraiso KH, Haarberg HE, Wood E, Rebecca VW, Chen YA, Xiang Y, Ribas A, Lo RS, Weber JS, Sondak VK, John JK, Sarnaik AA, Koomen JM, Smalley KS. The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. Clin Cancer Res. 2012; 18(9):2502-2514

Bussenius J, Blazey CM, Aay N, Anand NK, Arcalas A, Baik T, Bowles OJ, Buhr CA, Costanzo S, Curtis JK, DeFina SC, Dubenko L, Heuer TS, Huang P, Jaeger C, Joshi A, Kennedy AR, Kim AI, Lara K, Lee J, Li J, Lougheed JC, Ma S, Malek S, Manalo JC, Martini JF, McGrath G, Nicoll M, Nuss JM, Pack M, Peto CJ, Tsang TH, Wang L, Womble SW, Yakes M, Zhang W, Rice KD. Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90. Bioorg Med Chem Lett. 2012; 22(17): 5396-5404.

文献引用

1. Azimi A, Caramuta S, et al. "Targeting CDK2 overcomes melanoma resistance against BRAF and Hsp90 inhibitors." Mol Syst Biol. 2018 Mar 5;14(3):e7858. PMID:29507054

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt503.64
Cas No.1149705-71-4
FormulaC29H37N5O3
SynonymsXl 888, Xl888
Solubility≥18.2mg/mL in DMSO, <2.56 mg/mL in EtOH, <2.38 mg/mL in H2O
Chemical Name2-(butan-2-ylamino)-4-N-[(1R,5S)-8-[5-(cyclopropanecarbonyl)pyridin-2-yl]-8-azabicyclo[3.2.1]octan-3-yl]-5-methylbenzene-1,4-dicarboxamide
SDFDownload SDF
Canonical SMILESCCC(C)NC1=CC(=C(C=C1C(=O)N)C)C(=O)NC2CC3CCC(C2)N3C4=NC=C(C=C4)C(=O)C5CC5
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

细胞实验 [1]:

细胞系

耐Vemurafenib黑色素瘤细胞系

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

300 nM;72或144小时

实验结果

在耐Vemurafenib黑色素瘤细胞系中,XL888 (300 nM) 诱导细胞凋亡 (> 66%) 和线粒体膜电位减少。

动物实验 [1]:

动物模型

携带M229R细胞异种移植瘤的小鼠模型

给药剂量

100 mg/kg;口服给药;每周3次,持续15天

实验结果

在SCID小鼠中,XL888 (100 mg/kg) 显著诱导M229R细胞异种移植瘤消退。

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]. Paraiso KH, Haarberg HE, Wood E, Rebecca VW, Chen YA, Xiang Y, Ribas A, Lo RS, Weber JS, Sondak VK, John JK, Sarnaik AA, Koomen JM, Smalley KS. The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. Clin Cancer Res. 2012; 18(9):2502-2514.

生物活性

描述 XL-888是一种可口服的和ATP竞争性的热休克蛋白90(Hsp90)小分子抑制剂,IC50值为24 nM。
靶点 Hsp90          
IC50 24 nM          

质量控制

质量控制和MSDS

批次:

化学结构

XL-888

相关生物数据

XL-888