化合物AT7867 T6304

Product Introduction
Bioactivity


英文名: AT7867

描述: AT7867 是 ATP 竞争性的Akt1/Akt2/Akt3和p70S6K/PKA 抑制剂，IC50分别为 32、17、47 和 85、20 nM。

细胞实验: Cells are plated in 96-well microplates at 5 × 103 per well in medium supplemented with 10% fetal bovine serum and grown for 24 hours before treatment with AT7867. AT7867 or vehicle control is added to the cells for 72 hours. Following this, Alamar Blue solution is added. The IC50 value for AT7868 is calculated in GraphPad Prism using nonlinear regression analysis and a sigmoidal dose-response (variable slope) equation.(Only for Reference)

激酶实验: In vitro kinase assays : Kinase assays for Akt2, PKA, p70S6K, and CDK2/cyclin A are all carried out in a radiometric filter binding format. Assay reactions are set up in the presence of AT7867. For Akt2, the Akt2 enzyme and 25 μM Aktide-2T peptide (HARKRERTYSFGHHA) are incubated in 20 mM MOPS (pH 7.2), 25 mM β-glycerophosphate, 5 mM EDTA, 15 mM MgCl2, 1 mM sodium orthovanadate, 1 mM DTT, 10 μg/mL bovine serum albumin, and 30 μM ATP (1.16 Ci/mmol) for 4 hours. For PKA, the PKA enzyme and 50 μMpeptide (GRTGRRNSI) are incubated in 2 mM MOPS (pH 7.2), 25 mM β-glycerophosphate, 5 mM EDTA, 15 mM MgCl2, 1 mM orthovanadate, 1 mM DTT, and 40 μM ATP (0.88 Ci/mmol) for 20 minutes. For p70S6K, the p70S6K enzyme and 25 μMpeptide substrate (AKRRRLSSLRA) are incubated in 10 mM MOPS (pH 7), 0.2 mM EDTA, 1 mM MgCl2, 0.01% β-mercaptoethanol, 0.1 mg/mL bovine serum albumin, 0.001% Brij-35, 0.5% glycerol, and 15 μM ATP (2.3 Ci/mmol) for 60 min. For CDK2, the CDK2/cyclin A enzyme and 0.12 μg/mL histone H1 are incubated in 20 mM MOPS (pH 7.2), 25 mM β-glycerophosphate, 5 mM EDTA, 15 mM MgCl2, 1 mM sodium orthovanadate, 1 mM DTT, 0.1 mg/mL bovine serum albumin, and 45 μM ATP (0.78 Ci/mmol) for 4 hours. Assay reactions are stopped by adding an excess of orthophosphoric acid, and the stopped reaction mixture is then transferred to Millipore MAPH filter plates and filtered. The plates are then washed, scintillant is added, and radioactivity is measured by scintillation counting on a Packard TopCount. IC50 values are calculated from replicate curves using GraphPad Prism software. Akt1 and Akt3 enzyme assays are carried out.

体外活性: AT7867 also inhibits structurally related AGC kinases p70S6K and PKA with IC50 of 20 nM and 85 nM, respectively. AT7867 shows ATP-competitive activity to Akt2 with Ki of 18 nM. AT7867 exhibits antiproliferation in cell lines with PTEN or PIK3CA mutations and shows great potent to MES-SA, MDA-MB-468, MCF-7, HCT116 and HT29 with IC50 of 0.94 μM, 2.26 μM, 1.86 μM, 1.76 μM and 3.04 μM, respectively. AT7867 also suppresses the cell growth of U87 mg, PC-3 and DU145 cells with IC50 of 8.22 μM, 10.37 μM and 11.86 μM, respectively. AT7867 suppresses Akt activity by inhibiting phosphorylation of GSK-3β in human tumor cells with IC50 of 2-4 μM. AT7867 also induces the phosphorylation of the following Akt direct substrates including proapoptotic transcription factors FKHR (FoxO1a), FKHRL1 (FoxO3a) and the downstream target S6RP in U87 mg cells. [1]

体内活性: AT7867 shows bioavailability of 44% in mice by p.o. route. AT7867 could increase the cleaved PARP in MES-SA xenografts at 20 mg/kg i.p. or 90 mg/kg p.o. AT7867 significantly inhibits the tumor growth in MES-SA xenografts or U87 mg xenografts with T/C of 0.37 and 0.51, respectively. [1]

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 63 mg/mL (186.5 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : 5 mg/mL (14.79 mM)


关键字: Akt | PKA | Inhibitor | Ribosomal S6 Kinase (RSK) | inhibit | AT7867 | AT 7867 | S6K | Protein kinase A | Protein kinase B | PKB | AT-7867

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相关库: Anti-Liver Cancer Compound Library | Anti-Breast Cancer Compound Library | Anti-Cancer Compound Library | Bioactive Compounds Library Max | Neural Regeneration Compound Library | Inhibitor Library | Kinase Inhibitor Library | Tyrosine Kinase Inhibitor Library | Anti-Cancer Active Compound Library | Preclinical Compound Library

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