1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGSK2636771Cat. No.: HY-15245CAS No.: 1372540-25-4分式: CHFNO分量: 433.42作靶點: PI3K作通路: PI3K/Akt/mTOR儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 10.6 mg/mL (24.46 mM; Need ultrasonic and warm

2、ing)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.3072 mL 11.5362 mL 23.0723 mL5 mM 0.4614 mL 2.3072 mL 4.6145 mL10 mM 0.2307 mL 1.1536 mL 2.3072 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 GSK2636771有效，選擇性和可服的 PI3K 抑制劑，Ki和IC50分別為0.89，5.2 nM，p110和p110的選擇性900倍，p110同種型的

3、選擇性10倍。IC50 & Target p110體外研究GSK2636771 treatment causes cell viability significantly more decreased in the control cells (p110-reliantPTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines) than in PTEN-mutant and1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEPTEN wild-type EEC

4、cells. Inhibition of p110 by GSK2636771 or AZD6482 leads to a marked decrease ofAKT phosphorylation only in the control prostate and breast cancer cell lines, whereas only marginal effectson AKT activation are observed in EEC cells 1.體內(nèi)研究 GSK2636771 is a p110 inhibitor, and the p110 primes cells for

5、 response to growth factor stimulation. Whilep110 inhibition suppresses cell and tumor growth, dual targeting of p110/ enhances apoptosis andprovides sustained tumor response in mice model 2.PROTOCOLCell Assay 1 Cells are plated in 96-well microtiter plates at densities ranging from 1,500 to 15,000

6、cells/well, optimized foruntreated control cells to be 80-90% confluent at the endpoint of the experiment. After 24 h, cells are treatedwith serial dilutions (100 pM to 10 M) of the PI3K pathway inhibitors GDC-0941, A66, TGX-221,GSK2636771, AZD6482, Temsirolimus, AZD8055, PF-04691502, and of the MAP

7、K pathway inhibitorsAZD6244, PD0325901, AZD628, and PLX4032. Cell viability is assessed after 72 h of treatment byincubation with CellTiter Blue for 1.5 h. The drug concentration required for survival of 50% of cells relative tountreated cells is determined using GraphPad Prism version 5.0 d. Cell l

8、ines that fail to achieve the SF50 toa given drug are nominally assigned as the highest concentration screened (10 M). At least threeindependent experiments in triplicate per cell line/targeted drug are performed. Association between amutation and response to a targeted agent is determined using a F

9、ishers exact test, and a two-tailed Pvalue.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Mol Pharmacol. 2016 Dec;90(6):726-737. Harvard Medical School LINCS LIBRARYSee more customer valid

10、ations on HYPERLINK / www.MedChemEREFERENCES1. Weigelt B, et al. PI3K pathway dependencies in endometrioid endometrial cancer cell lines. Clin Cancer Res. 2013, 19(13), 3533-3544.2. Hosford SR, et al. Combined inhibition of both p110 and p110 isoforms of phosphatidylinositol 3-kinase is required for sustainedtherapeutic effect in PTEN-deficient, ER+ breast cancer. Clin Cancer Res. 2016 Nov 30McePdfHeightCaution: Product has not been fully