XL888

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。

XL888  纯度: 99.62%

XL888 是一种热休克蛋白 90 (HSP90) 抑制剂,IC50 值为 24 nM。

XL888

XL888 Chemical Structure

CAS No. : 1149705-71-4

规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ¥1828 In-stock
1 mg ¥550 In-stock
5 mg ¥1650 In-stock
10 mg ¥2650 In-stock
25 mg ¥5300 In-stock
50 mg ¥9400 In-stock
100 mg   询价  
200 mg   询价  

* Please select Quantity before adding items.

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生物活性

XL888 is a heat shock protein-90 (HSP90) inhibitor, with an IC50 of 24 nM.

IC50 & Target[3]

HSP90

24 nM (IC50)

体外研究
(In Vitro)

XL888 is a heat shock protein-90 (HSP90) inhibitor. Treatment with XL888 leads to dose dependent decreases in the growth of all the cell lines with no significant difference in IC50 values observed between the naive and resistance pairs of cell lines (t=0.25, p=0.82). Treatment of all of the vemurafenib resistant cell lines with XL888 (300 nM) induces high levels (>66%) of apoptosis, caspase-3 cleavage and loss of mitochondrial membrane potential (TMRM) in every cell line tested. Treatment of cell lines that are naïve, intrinsically resistant and with acquired vemurafenib resistance with XL888 (300 nM) leads to robust time-dependent increases in the expression of HSP70 isoform 1 (HSP71)[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)

Treatment of the established M245 tumors with XL888 (125 mg/kg 3× week) leads to a significant slowing of tumor growth (P=0.017) without any effect upon animal weights. Analysis of xenograft specimens by LC-MRM shows a marked increase in intratumoral HSP70 expression following XL888 treatment[1]. It is noted that the XL888 is well tolerated by the mice, with no significant alterations in body weigh observed over the study period. LC-MRM mediated analysis of xenograft samples following 15-days of XL888 treatment shows a robust (8.6-fold) increase in intratumoral HSP70 expression compare to controls[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.

Clinical Trial

分子量

503.64

Formula

C29H37N5O3

CAS 号

1149705-71-4

运输条件

Room temperature in continental US; may vary elsewhere.

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

DMSO : 50 mg/mL (99.28 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.9855 mL 9.9277 mL 19.8555 mL
5 mM 0.3971 mL 1.9855 mL 3.9711 mL
10 mM 0.1986 mL 0.9928 mL 1.9855 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: ≥ 1.25 mg/mL (2.48 mM); Clear solution

    此方案可获得 ≥ 1.25 mg/mL (2.48 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 12.5 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

  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 1.25 mg/mL (2.48 mM); Clear solution

    此方案可获得 ≥ 1.25 mg/mL (2.48 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 12.5 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
  • 3.

    请依序添加每种溶剂: 10% DMSO    90% corn oil

    Solubility: ≥ 1.25 mg/mL (2.48 mM); Clear solution

    此方案可获得 ≥ 1.25 mg/mL (2.48 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 12.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*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]. Haarberg HE, et al. Inhibition of Wee1, AKT, and CDK4 underlies the efficacy of the HSP90 inhibitor XL888 in an in vivo model of NRAS-mutant melanoma. Mol Cancer Ther. 2013 Jun;12(6):901-12.

    [2]. Paraiso KH, et al. The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. Clin Cancer Res. 2012 May 1;18(9):2502-14.

    [3]. Bussenius J, et al. Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5396-404.

Cell Assay
[1]

Cells are plated in 96-well plates at 2×104 per well. Media with vehicle (DMSO) or XL888 (10, 30, 100 or 300 nM) is added the following day and replaced twice a week. After 4 weeks the plates are stained with crystal violet[1].

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]

BALB SCID mice are subcutaneously injected with 2.5×106 cells per mouse and grown to approximately 100 mm3 prior to dosing. Mice are treated with either XL888 100 mg/kg (n=5) or an equivalent volume of vehicle (10 mM HCl), 3× per week by oral gavage. Mouse weights and tumor volumes (L×W2/2) are measured 3× per week. Upon completion of the experiment, vehicle and drug treated tumor biopsies are processed for LC-MRM analysi[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]. Haarberg HE, et al. Inhibition of Wee1, AKT, and CDK4 underlies the efficacy of the HSP90 inhibitor XL888 in an in vivo model of NRAS-mutant melanoma. Mol Cancer Ther. 2013 Jun;12(6):901-12.

    [2]. Paraiso KH, et al. The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. Clin Cancer Res. 2012 May 1;18(9):2502-14.

    [3]. Bussenius J, et al. Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5396-404.

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