|(S)-4-(2-(4-氨基-1,2,5-额二唑-3-基)-1-乙基-7-(哌啶-3-基甲氧基)-1H-咪唑并[4,5-c]吡啶-4-基)-2-甲基丁-3-炔-2-醇|CsnPharm

CAS No.: 937174-76-0

GSK-690693 Catalog No. CSN13165

Synonyms: GSK690693

GSK690693 is a pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 2 nM/13 nM/9 nM, also sensitive to the AGC kinase family: PKA, PrkX and PKC isozymes.

规格	价格	促销价格	库存	数量

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

加入购物车大规格询价

加入收藏

产品咨询

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

生物活性

靶点 Akt1

IC50:2nM Akt2

IC50:13nM Akt3

IC50:9nM
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

Cell Data

Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
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

动物研究

剂量

Mice^[3]: 30 mg/kg (i.p,)

给药途径

i.p.

动物药代数据

Animal	Rats^[4]	Dogs^[4]	Monkeys
Dose	10.6 mg/kg	4.2 mg/kg	4.3 mg/kg
Administration	i.v.	i.v.	i.v.
C_max	2.13 ± 0.19 μg/ml	1.30 ± 0.11 μg/ml	1.50 ± 0.10 μg/ml
T_1/2	8.92 ± 1.03 h	3.50 ± 0.33 h	5.52 ± 0.43 h
Protein binding (free drug %)	j
AUC_0→t	3.15 ± 0.32 (μg·h)/ml (0-inf)	2.01 ± 0.11 (μg·h)/ml (0-inf)	3.25 ± 0.67 (μg·h)/ml (0-inf)
CL	56.7 ± 5.5 (ml·min)/kg	34.6 ± 2.0 (ml·min)/kg	22.5 ± 4.3 (ml·min)/kg
Vss	15.2 ± 1.3 L/kg	5.29 ± 0.24 L/kg	6.54 ± 0.89 L/kg

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 ... more >> 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 Collapse <<
NCT00666081	Cancer	Phase 1	Withdrawn(Study Cancelled befo... more >>re enrollment) Collapse <<	December 2009	-

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.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.3503 mL
- 11.7514 mL
- 23.5029 mL
- 5 mM
- 0.4701 mL
- 2.3503 mL
- 4.7006 mL
- 10 mM
- 0.2350 mL
- 1.1751 mL
- 2.3503 mL

技术信息

CAS号

937174-76-0

储存条件

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

液体: -20°C:3-6 月 -80°C:12月

分子式

C21H27N7O3

运输

蓝冰

分子量

425.48

别名

GSK690693

溶解度

DMSO	40.0 mg/mL (94.0 mM)

动物实验配方

5% DMSO+40%PEG300+5% tween80+50% water

3 mg/mL

大规格询价

号为必填项

姓名: 邮箱: 手机号:

留言:

提交

靶点	Description	IC50
Akt1		IC50:2nM
Akt2		IC50:13nM
Akt3		IC50:9nM

GSK-690693 Catalog No. CSN13165

靶点选择性

请登录您的专属账户

确认信息