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GSK2636771
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
GSK2636771图片
CAS NO:1372540-25-4
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
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产品介绍
理化性质和储存条件

Molecular Weight (MW)

433.42

Formula

C22H22F3N3O3

CAS No.

1372540-25-4 freebase

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 28 mg/mL (64.6 mM)

Water:<1 mg/mL

Ethanol: <1 mg/mL

SMILES

O=C(C1=C2C(N(CC3=CC=CC(C(F)(F)F)=C3C)C(C)=N2)=CC(N4CCOCC4)=C1)O

Synonym/Chemical Name

GSK2636771; GSK-2636771; GSK 2636771; 2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylbenzimidazole-4-carboxylic acid

实验参考方法

In Vitro

Kinase Assay: GSK2636771 is a potent, selective and oral inhibitor of PI3Kβ with a Ki of 0.89 nM and an IC50 of 5.2 nM, showing 900-fold selectivity over p110α and p110γ, and 10-fold selectivity over p110δ isoforms.

Cell Assay: Cells (p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines) are plated in 96-well microtiter plates at densities ranging from 1,500 to 15,000 cells/well, optimized for untreated control cells to be 80-90% confluent at the endpoint of the experiment. After 24 h, cells are treated with serial dilutions (100pM to 10μM) of GSK2636771. Cell viability is assessed after 72 h of treatment by incubation with CellTiter Blue for 1.5 h. The drug concentration requires for survival of 50% of cells relative to untreated cells (surviving fraction 50, SF50) is determined using GraphPad Prism version 5.0d. Cell lines that fails to achieve the SF50 to a given drug are nominally assigned as the highest concentration screened (i.e. 10μM). At least three independent experiments in triplicate per cell line targeted drug are performed. Association between a mutation and response to a targeted agent is determined using a Fisher’s exact test (GraphPad Prism), and a two-tailed P value<0.05 is considered statistically significant.

GSK-2636771 shows selectively inhibitory activity in PTEN null cell lines (human prostate adenocarcinoma PC-3 and breast cancer HCC70) with EC50 of 36 nM and 72 nM, respectively. GSK2636771 significantly decreases cell viability in p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines, and leads to a marked decrease of AKT phosphorylation only in the control prostate and breast cancer cell lines.

In Vivo

GSK-2636771 decreases phosphorylated protein kinase Akt (Ser473) levels in these xenograft models. GSK-2636771 (100 mg/kg) do not increase glucose/insulin levels in mice.

Animal model

Mice

Formulation & Dosage

100 mg/kg

References

Clin Cancer Res. 2013 Jul 1;19(13):3533-44.

生物活性


Clin Cancer Res. 2013, 19(13), 3533-3544.



PI3K inhibition-induced Rb inactivation predicts subsequent apoptosis in PTEN-deficient, ER+ breast cancer cells. Clin Cancer Res. 2017 Jun 1;23(11):2795-2805.


PI3K inhibition-induced Rb inactivation predicts subsequent apoptosis in PTEN-deficient, ER+ breast cancer cells. Clin Cancer Res. 2017 Jun 1;23(11):2795-2805.