靶向变构位点的变构激酶抑制剂的研究进展

Advances in allosteric kinases inhibitors that targeting the allosteric sites

目的对变构激酶抑制剂的特点及研究现状进行综述,期望能为高效的变构激酶抑制剂的研发提供参考。方法查阅国内外相关文献,对蛋白激酶抑制剂的结合方式、结构特点、研究进展等方面进行总结和分析。结果变构调节作为一种高效调节机制,可通过结合于不同催化位点的变构位点使蛋白质的构象发生变化而发挥调节活性,从而保证细胞正常功能运行。由于不与激酶催化位点重合,靶向蛋白激酶结构中的变构位点能够获得较传统ATP竞争性抑制剂具有更高选择性和活性的变构激酶抑制剂。结论基于变构调节机制,靶向变构位点的变构激酶抑制剂可作为新药开发的重要策略。

Objective To review the development of allosteric inhibitors based on chemical structures in aim of provide reference for developing allosteric inhibitors with better properties.Methods Referring to relevant literatures,the classification of kinases inhibitors is covered.Chemical structures,binding modes and interactions of allosteric inhibitors of kinases are described briefly.Results Allostery is the inherent property and effective regulatory mechanisms in cells.Binding to an allosteric site which is pographically distinct from orthoseric site,the allosteric ligand change the conformation of receptor/protein in controlling of several biomolecule functions.Targeting the allosteric sites in kinases give way to develop allosteric inhibitors with higher selectivity and more potent activity compared to traditional ATP competitive inhibitors.Conclusion Based on allostery,the allosteric kinase inhibitors become an important and effective strategy for drug development.