产品说明书

GSK-690693

Print
Chemical Structure| 937174-76-0 同义名 : -
CAS号 : 937174-76-0
货号 : A111141
分子式 : C21H27N7O3
纯度 : 99%+
分子量 : 425.484
MDL号 : MFCD14105605
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 18 mg/mL(42.3 mM)，配合低频超声，并水浴加热至45℃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

H2O: 5 mg/mL(11.75 mM)，配合低频超声，并调节pH至5
动物实验配方：

5% DMSO+40%PEG300+5% tween80+50% water 3 mg/mL

生物活性
靶点

  • Akt3

    Akt3, IC50:9 nM

  • Akt1

    Akt1, IC50:2 nM

  • Akt2

    Akt2, IC50:13 nM
描述 AKT is the central node of PI3K/AKT/mTOR pathway. The PH domain and ATP-competitive site are the main target site for research of new compound[1]. GSK690693 is an ATP-competitive pan AKT inhibitor with IC50 values of 2, 13 and 9nM for AKT 1, 2, and 3, respectively. Treatment with GSK690693 on concentration of 0.01-10uM cause decreased phosphorylation level of GSK3, p70S6K, and PRAS40 in BT474 breast tumor cells in a dose-dependent manner. GSK690693 can induce accumulation of the FOXO3A, an Akt downstream substrate, in the nucleus at concentration >1uM. In growth inhibition studies, cell lines with higher level of p-AKT showed more sensitivity to GSK690693, such as HCC1954, ZR-75-1, BT474 and LNCaP, etc.. In vivo studies showed maximal tumor growth inhibition of 58% to 75% at the end of dosing period with 30mg/kg/day dose of GSK690693 (i.p.) for 21 days in mice bearing established SKOV-3 ovarian, LNCaP prostate, BT474 and HCC-1954 breast carcinoma xenografts[2].
作用机制 GSK690693 is an ATP-competitive AKT inhibitor[2].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
HFF cells Cytotoxic assay Cytotoxicity against HFF cells, IC50=16.3 μM 18800763
human BT474 cells Proliferation assay Antiproliferative activity against human BT474 cells, IC50=50 nM 18800763
human LNCaP cells Proliferation assay Antiproliferative activity against human LNCaP cells, IC50=20 nM 18800763
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00493818 Cancer Phase 1 Terminated - United States, Indiana ... 展开 >> GSK Investigational Site Indianapolis, Indiana, United States, 46202 United States, Michigan GSK Investigational Site Detroit, Michigan, United States, 48201 United States, North Carolina GSK Investigational Site Durham, North Carolina, United States, 27710 收起 <<
NCT00666081 Cancer Phase 1 Withdrawn(Study Cancelled befo... 展开 >>re enrollment) 收起 << December 2009 -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.35mL

0.47mL

0.23mL

11.75mL

2.35mL

1.18mL

23.50mL

4.70mL

2.35mL
参考文献

[1]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.

[2]Rhodes N, Heerding DA, et al. Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity. Cancer Res. 2008 Apr 1;68(7):2366-74.

[3]Altomare DA, Zhang L, et al. GSK690693 delays tumor onset and progression in genetically defined mouse models expressing activated Akt. Clin Cancer Res. 2010 Jan 15;16(2):486-96.

[4]Heerding DA, Rhodes N, et al. Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase. J Med Chem. 2008 Sep 25;51(18):5663-79.