Ipatasertib

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Chemical Structure| 1001264-89-6 同义名 : GDC-0068;RG7440
CAS号 : 1001264-89-6
货号 : A115731
分子式 : C24H32ClN5O2
纯度 : 99%+
分子量 : 457.996
MDL号 : MFCD22124514
存储条件：

Pure form Keep in dark place,Sealed in dry,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 200 mg/mL(436.68 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

H2O: 3 mg/mL(6.55 mM)，配合低频超声，并水浴加热至45℃助溶
动物实验配方：
生物活性
靶点

  • Akt3

    Akt3, IC50:8 nM

  • Akt1

    Akt1, IC50:5 nM

  • Akt2

    Akt2, IC50:18 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]. GDC-0068 (Ipatasertib) is an ATP-competitive pan Akt inhibitor with IC50 values of 5 nM, 18 nM and 8 nM on AKT 1, 2 and 3 isoforms, respectively[2]. Treatment of GDC-0068 on concentration of 0.1 - 25 μM caused decreased phosphorylation of the downstream targets of AKT, such as FoxO1 and FoxO3a, 4EBP1 and S6 in a dose- and time-dependent manner in PC-3, BT474M1, and IGROV-1 cell lines, accompanied by feedback increase in AKT phosphorylation. Treatment of GDC-0068 on concentration of 1 – 10 μM can induce G1-arrest (including in PC-3 cells) and increase in apoptotic and necrotic populations in a dose- and time-dependent manner in BT474M1 and MCF7-neo/HER2 cells, but not in PC-3 cells. In growth inhibition assay, cell lines with high Akt activity show more sensitivity to GDC-0068. GDC-0068 showed good pharmacokinetics and pharmacodynamics in xenograft models. The level of pPRAS40-T246 in LNCaP tumors at 1 and 4 hours after a single dose of GDC-0068 at 12.5, 25, 50, or 100 mg/kg decreased in a dose-dependent manner. GDC-0068 on dose of 50 mg/kg in combination with docetaxel induced tumor regression and stasis in the PC-3 and MCF7-neo/HER2 xenograft models[3]. The clinical trials of GDC-0068, including a completed phase 2 study of combination with paclitaxel as neoadjuvant treatment for participants with early stage triple negative breast cancer, have been done (see in https://clinicaltrials.gov/).
作用机制 GDC-0068 is an ATP-competitive AKT inhibitor.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
BT474M1 0.0038-2.5 μM Function Assay 1 h induces a dose-dependent increase in Akt phosphorylation at both Thr308 (T308) and Ser473 23287563
BT474M1 1/5/10 μM Growth Inhibition Assay 24/48/72 h dose-dependently increases the G0–G1 phase population  23287563
BT474M1 1/5/10 μM Apoptosis Assay 15/48/72 h causes a dose- and time-dependent increase in apoptotic and necrotic populations 23287563
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.18mL

0.44mL

0.22mL

10.92mL

2.18mL

1.09mL

21.83mL

4.37mL

2.18mL
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]Blake JF, Xu R, et al. Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors. J Med Chem. 2012 Sep 27;55(18):8110-27. Epub 2012 Sep 18.

[3]Lin J, Sampath D, et al. Targeting activated Akt with GDC-0068, a novel selective Akt inhibitor that is efficacious in multiple tumor models. Clin Cancer Res. 2013 Apr 1;19(7):1760-72.

[4]EP2928488A1