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AT7867

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品牌名称:$brandModel.Title(进口品牌)型号: 原产地:美洲 发布时间:2021/7/24更新时间:2024/1/2

产品摘要:AT7867 是一种 ATP 竞争性的 Akt1/Akt2/Akt3 和 p70S6K/PKA 抑制剂,IC50 分别为 32 nM/17 nM/47 nM 和 85 nM/20 nM。

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AT7867

CAS No. : 857531-00-1

MCE 站:AT7867

产品活性:AT7867 是一种 ATP 竞争性的 Akt1/Akt2/Akt3p70S6K/PKA 抑制剂,IC50 分别为 32 nM/17 nM/47 nM 和 85 nM/20 nM。

研究领域:PI3K/Akt/mTOR  |  Stem Cell/Wnt  |  Protein Tyrosine Kinase/RTK  |  MAPK/ERK Pathway

作用靶点:Akt  |  PKA  |  Ribosomal S6 Kinase (RSK)

In Vitro: The inhibition of AKT2 by AT7867 is shown to be ATP-competitive with a Ki of 18nM. AT7867 also displays potent activity against the structurally related AGC kinases p70S6K and PKA, but shows a clear window of selectivity against kinases from other kinase sub-families. In vitro growth inhibition studies show that AT7867 blocks proliferation in a number of human cancer cell lines. AT7867 appears to be most potent at inhibiting proliferation in MES-SA uterine, MDA-MB-468 and MCF-7 breast, and HCT116 and HT29 colon lines (IC50 values range from 0.9-3 μM), and least effective in the two prostate lines tested (IC50 values range from 10-12 μM) .

In Vivo: In vivo: Following oral administration at 20 mg/kg, the elimination of AT7867 from plasma appears to be similar to that observed after i.v. administration. Plasma levels of AT7867 remain above 0.5 μM for at least 6 hours following an oral dose of 20 mg/kg. Assuming linear pharmacokinetics following i.v. administration, the bioavailability by the oral route is calculated to be 44%. In vivo pharmacodynamic (PD) biomarker studies are therefore performed with this model. Following pharmacokinetic and tolerability studies, doses of AT7867 (90 mg/kg p.o. or 20 mg/kg i.p.) are administered to athymic mice bearing MES-SA tumors and the phosphorylation status of GSK3β and S6RP in tumors is monitored over time. Clear inhibition of phosphorylation of the two markers of pathway activity is seen at 2 and 6 hours following treatment with AT7867. By 24 hours, total levels of both GSK3β and S6RP are greatly reduced.

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