开发同工型选择性 PI3-激酶抑制剂作为阐明 PI3K 通路的药理学工具。
Development of isoform selective PI3-kinase inhibitors as pharmacological tools for elucidating the PI3K pathway.
机构信息
Novartis Institutes for Biomedical Research, Respiratory Disease Area, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK.
出版信息
Bioorg Med Chem Lett. 2012 Sep 1;22(17):5445-50. doi: 10.1016/j.bmcl.2012.07.042. Epub 2012 Jul 17.
Using a parallel synthesis approach to target a non-conserved region of the PI3K catalytic domain a pan-PI3K inhibitor 1 was elaborated to provide alpha, delta and gamma isoform selective Class I PI3K inhibitors 21, 24, 26 and 27. The compounds had good cellular activity and were selective against protein kinases and other members of the PI3K superfamily including mTOR and DNA-PK.
采用平行合成方法针对 PI3K 催化结构域的非保守区域进行靶向研究，设计并合成了 pan-PI3K 抑制剂 1，进一步得到对 alpha、delta 和 gamma 同工型具有选择性的 Class I PI3K 抑制剂 21、24、26 和 27。这些化合物具有良好的细胞活性，对蛋白激酶和其他 PI3K 超家族成员（包括 mTOR 和 DNA-PK）具有选择性。
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