选择性的激酶ATP竞争性抑制剂设计研究进展

Progress in the design of selective ATP-competitive kinase inhibitors

激酶在细胞的生命过程中起着至关重要的作用,其功能异常会导致包括肿瘤在内的许多重大疾病的发生。针对疾病相关的激酶靶标,研发ATP竞争性的小分子激酶抑制剂成为当前的热点。但激酶催化域的结构和序列高度保守,使得许多激酶抑制剂的选择性都比较低。近年来,随着结构生物学和计算机辅助药物分子设计技术的进步,选择性的ATP竞争性激酶抑制剂的研发取得了很大的进展,本文拟就近年来选择性的激酶抑制剂设计研究进展作一综述。

Kinases play crucial roles in the life of cell.Their functional abnormity usually leads to many human major diseases including tumors.The prospecting of ATP-competitive small-molecule kinase inhibitors targeting kinases of therapeutic interest has become the focus of researches.Due to the high conservation of the catalytic domain of kinases,the selectivity of kinase inhibitors is poor in general.However,along with the development of structural biology and computer-aided drug design,great progress in the research of selective,ATP-competitive kinase inhibitors has been achieved in recent years.In this account,the review has been made on the development of the design of selective kinase inhibitors.