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Chemical Structure| 1047634-65-0 同义名 : GSK2141795;GSK795
CAS号 : 1047634-65-0
货号 : A202830
分子式 : C18H16Cl2F2N4O2
纯度 : 99%+
分子量 : 429.248
MDL号 : MFCD28144686
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(116.48 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • Akt3

    Akt3, IC50:38 nM

  • Akt1

    Akt1, IC50:180 nM

  • Akt2

    Akt2, IC50:328 nM
描述 AKT is the central node of the PI3K/AKT/ mTOR pathway. The PH domain and ATP-competitive site are the main target site for research of new compound[2]. GSK2141795 is an ATP-competitive pan AKT inhibitor with Ki values of 180, 328 and 38nM for AKT 1, 2 and 3 (determined by the kinobead competition binding assay)[1]. Treatment of GSK2141795 on concentration of 1-10 μM can induce G1-arrest and decrease the phosphorylation level of multiple AKT substrate including PRAS40, FOXO and Caspase 9 in BT474 and LNCaP cell lines in a concentration-dependent manner, accompanied by feedback increase in AKT phosphorylation. In cell growth inhibition study, overall 81% of the hematological cell lines were sensitive to GSK2141795 (EC50 <1 uM). Among solid tumor cell lines, 36% had EC50<1 μM in response to GSK2141795. Cell lines containing activating mutations to KRAS, NRAS or BRAF showed more resistence to GSK2141795. Mice bearing SKOV3 ovarian tumor xenografts orally treated with 10, 20 and 30 mg/kg GSK2141795, once daily for 21 days, displayed a 73, 85 or 93% TGI, respectively[3]. Several clinical trials of GSK2141795, including a phase 1 study of GSK2141795 of treatment for solid tumors, have been completed (see in https://clinicaltrials.gov/).
作用机制 GSK2141795 is an ATP-competitive AKT inhibitor.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.33mL

0.47mL

0.23mL

11.65mL

2.33mL

1.16mL

23.30mL

4.66mL

2.33mL
参考文献

[1]Pachl F, Plattner P, et al. Characterization of a chemical affinity probe targeting Akt kinases. J Proteome Res. 2013 Aug 2;12(8):3792-800.

[2]Huck BR, Mochalkin I, et al. Recent progress towards clinically relevant ATP-competitive Akt inhibitors. Bioorg Med Chem Lett. 2017 Jul 1;27(13):2838-2848.

[3]Dumble M, Crouthamel MC, 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.