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AT7867

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Chemical Structure| 857531-00-1 同义名 : -
CAS号 : 857531-00-1
货号 : A151784
分子式 : C20H20ClN3
纯度 : 99%+
分子量 : 337.846
MDL号 : MFCD18384971
存储条件：

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

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(148 mM)，配合低频超声，并水浴加热至45℃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
动物实验配方：
生物活性
靶点

  • Akt3

    Akt3, IC50:47 nM

  • Akt1

    Akt1, IC50:32 nM

  • Akt2

    Akt2, IC50:17 nM
描述 The protein kinase B (AKT) is a serine/threonine kinase that plays a pivotal role in tumor cell growth, malignant transformation, and chemoresistance. AT7867 is a potent inhibitor of three isoforms of AKT (AKT1, AKT2, and AKT3), the downstream kinase p70S6K, and PKA with IC50 values of 32, 17, 47, 20, and 85nM, respectively. AT7867 potently binds to AK2 in a ATP-competitive manner with a Ki value of 18nM. AT7867 inhibited the proliferation of multiple human cancer cell lines, including MES-SA, MDA-MB-468, MCF-7, U87MG, PC-3, DU145, HCT116, and HT29, with IC50 values in the range of 0.9–12µM. It also exerts an equipotent inhibitory effect on GSK3β phosphorylation across multiple cancer cell lines with IC50 values ranging from 2–4μM. The treatment of U87MG human glioblastoma cells with AT7867 induces apoptosis and suppressed AKT signaling in a concentration- and time-dependent manner. The administration of AT7867 (90mg/kg p.o. or 20mg/kg i.p.) significantly inhibited the phosphorylation of GSK3β and S6RP in mice bearing MES-SA tumors at 2 and 6 h following treatment. Mice treated with AT7867 at 20mg/kg i.p. showed a T/C ratio (tumor volume in treated mice versus control mice) of 0.37 on day 12. The T/C ratio in the group administered with AT7867 at 90mg/kg p.o. was 0.38 on day 10. [2]
作用机制 AT7867 binds to the ATP site of AK2, forming electrostatic interactions with the ribose site, hydrogen-bonding interactions with the kinase hinge region, and hydrophobic contacts with a lipophilic pocket in the glycine-rich loop.[2]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.96mL

0.59mL

0.30mL

14.80mL

2.96mL

1.48mL

29.60mL

5.92mL

2.96mL
参考文献

[1]Grimshaw KM, Hunter LJ, et al. AT7867 is a potent and oral inhibitor of AKT and p70 S6 kinase that induces pharmacodynamic changes and inhibits human tumor xenograft growth. Mol Cancer Ther. 2010 May;9(5):1100-10.

[2]Grimshaw KM, Hunter LJ, Yap TA, et al. AT7867 is a potent and oral inhibitor of AKT and p70 S6 kinase that induces pharmacodynamic changes and inhibits human tumor xenograft growth. Mol Cancer Ther. 2010;9(5):1100‐1110. doi:10.1158/1535-7163.MCT-09-0986