Afuresertib
(Synonyms: GSK2110183) 目录号 : GC16475
A pan-Akt inhibitor
Cas No.:1047644-62-1
Sample solution is provided at 25 µL, 10mM.
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Afuresertib (GSK2110183) 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].
Afuresertib (GSK2110183) 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].
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[1].
References:
[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.
Cell experiment: | 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]. |
References: [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. | |
| Cas No. | 1047644-62-1 | SDF | |
| 别名 | GSK2110183 | ||
| 化学名 | N-[(2S)-1-amino-3-(3-fluorophenyl)propan-2-yl]-5-chloro-4-(4-chloro-2-methylpyrazol-3-yl)thiophene-2-carboxamide | ||
| Canonical SMILES | CN1C(=C(C=N1)Cl)C2=C(SC(=C2)C(=O)NC(CC3=CC(=CC=C3)F)CN)Cl | ||
| 分子式 | C18H17Cl2FN4OS | 分子量 | 427.32 |
| 溶解度 | ≥ 96mg/mL in DMSO | 储存条件 | Store at -20°C, protect from light, stored under nitrogen |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3402 mL | 11.7008 mL | 23.4017 mL |
| 5 mM | 0.468 mL | 2.3402 mL | 4.6803 mL |
| 10 mM | 0.234 mL | 1.1701 mL | 2.3402 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet