Afuresertib hydrochloride(Synonyms: GSK2110183 hydrochloride)

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。

Afuresertib hydrochloride (Synonyms: GSK2110183 hydrochloride) 纯度: 98.02%

Afuresertib hydrochloride (GSK 2110183 hydrochloride) 是一个口服有效的,ATP 竞争性的选择性 pan-Akt 抑制剂,作用于 Akt1/Akt2/Akt3Ki 值分别为 0.08/2/2.6 nM。

Afuresertib hydrochloride(Synonyms: GSK2110183 hydrochloride)

Afuresertib hydrochloride Chemical Structure

CAS No. : 1047645-82-8

规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ¥1122 In-stock
2 mg ¥800 In-stock
5 mg ¥1100 In-stock
10 mg ¥1650 In-stock
50 mg ¥5200 In-stock
100 mg ¥7900 In-stock
200 mg   询价  
500 mg   询价  

* Please select Quantity before adding items.

Afuresertib hydrochloride 相关产品

相关化合物库:

  • Drug Repurposing Compound Library Plus
  • Clinical Compound Library Plus
  • Bioactive Compound Library Plus
  • Cell Cycle/DNA Damage Compound Library
  • Epigenetics Compound Library
  • Kinase Inhibitor Library
  • PI3K/Akt/mTOR Compound Library
  • Stem Cell Signaling Compound Library
  • TGF-beta/Smad Compound Library
  • Anti-Cancer Compound Library
  • Clinical Compound Library
  • Autophagy Compound Library
  • Anti-Aging Compound Library
  • Drug Repurposing Compound Library
  • Differentiation Inducing Compound Library
  • Reprogramming Compound Library
  • Oxygen Sensing Compound Library
  • Glycolysis Compound Library
  • Cytoskeleton Compound Library
  • Orally Active Compound Library
  • Glutamine Metabolism Compound Library
  • Anti-Breast Cancer Compound Library
  • Anti-Lung Cancer Compound Library
  • Anti-Pancreatic Cancer Compound Library
  • Anti-Blood Cancer Compound Library
  • Anti-Cancer Metabolism Compound Library
  • Anti-Obesity Compound Library
  • Angiogenesis Related Compound Library
  • Glucose Metabolism Compound Library
  • Anti-Liver Cancer Compound Library
  • Rare Diseases Drug Library
  • Anti-Colorectal Cancer Compound Library

生物活性

Afuresertib hydrochloride (GSK 2110183 hydrochloride) is an orally bioavailable, selective, ATP-competitive and potent pan-Akt kinase inhibitor with Kis of 0.08/2/2.6 nM for Akt1/Akt2/Akt3 respectively[1][2].

IC50 & Target[2]

Akt

 

Akt1

0.08 nM (Ki)

Akt2

2 nM (Ki)

Akt3

2.6 nM (Ki)

Akt1 E17K mutant

0.2 nM (IC50)

PKCη

210 nM (IC50)

PKC-βI

430 nM (IC50)

ROCK

100 nM (IC50)

PKCθ

510 nM (IC50)

体外研究
(In Vitro)

Afuresertib (GSK 2110183) exhibits favorable tumor-suppressive effects on malignant pleural mesothelioma (MPM) cells. Afuresertib significantly increases caspase-3 and caspase-7 activities and apoptotic cell number among ACC-MESO-4 and MSTO-211H cells. Afuresertib strongly arrests the cell cycle in the G1 phase.
Western blotting analysis shows that Afuresertib increases the expression of p21WAF1/CIP1 and decreases the phosphorylation of Akt substrates, including GSK-3β and FOXO family proteins. Afuresertib-induced p21 expression promotes G1 phase arrest by inducing FOXO activity. Afuresertib significantly enhances cisplatin-induced cytotoxicity. Afuresertib modulates the expression E2F1 and MYC, which are associated with fibroblast core serum response[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.

体内研究
(In Vivo)

Mice bearing BT474 breast tumor xenografts are dosed orally with either vehicle or GSK2110183 at 10, 30 or 100 mg/kg daily for 21 days which result in 8, 37 and 61% TGI, respectively. Mice tolerated GSK2110183 well, with 1-3% body weight loss reported after 5 days of dosing which recover over the course of the study. Other tumor xenograft models which possess an activation of the Akt pathway are explored to further demonstrate compound efficacy. Mice treated with GSK2110183 at 10, 30 and 100 mg/kg result in 23, 37 and 97% TGI, respectively, of SKOV3 xenografts[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

463.78

Formula

C18H18Cl3FN4OS

CAS 号

1047645-82-8

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

-20°C, protect from light, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

溶解性数据
In Vitro: 

DMSO : 100 mg/mL (215.62 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.1562 mL 10.7810 mL 21.5619 mL
5 mM 0.4312 mL 2.1562 mL 4.3124 mL
10 mM 0.2156 mL 1.0781 mL 2.1562 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 (protect from light, stored under nitrogen)。-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: ≥ 2.5 mg/mL (5.39 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.39 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 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: ≥ 2.5 mg/mL (5.39 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.39 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 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: ≥ 2.5 mg/mL (5.39 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.39 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 25.0 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]. Yamaji M, et al. Novel ATP-competitive Akt inhibitor Afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659.

    [2]. Dumble M, et al. Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor. PLoS One. 2014 Jun 30;9(6):e100880

Cell Assay
[1]

MPM cells are seeded in 96-well plates (cell density, 2.5×103 cells/well) and are incubated for 24 h at 37°C. Next, the cells are incubated in a medium containing indicated concentrations of Akt inhibitors (e.g., Afuresertib ; 50, 20, 10, 5, 2, 1, 0.5, 0.2, 0.1, and 0.01 μM) for 72 h. Next, MTT solution is added to each well, and the cells are incubated for 4 h. Finally, the cells are incubated overnight with lysis buffer (10% SDS in 0.01 mol/L hydrogen chloride). Absorbance is measured at 550 nm using SpectraMAX M5 spectrophotometer[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.

参考文献
  • [1]. Yamaji M, et al. Novel ATP-competitive Akt inhibitor Afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659.

    [2]. Dumble M, et al. Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor. PLoS One. 2014 Jun 30;9(6):e100880

所有产品仅用作科学研究或药证申报,我们不为任何个人用途提供产品和服务