盘状结构域受体(DDRs)抑制剂的研究进展

Research progress of discoidin domin receptors(DDRs) inhibitors

盘状结构域受体(DDRs)为跨膜受体酪氨酸激酶超家族的成员,可参与细胞增殖、迁移、粘附和基质重塑等多种细胞过程。DDRs功能失调与纤维化、动脉粥样硬化及癌症等多种疾病的发生发展密切相关,因此,DDRs成为药物研发新的潜在分子靶标。鉴于DDRs与受体酪氨酸激酶的ATP结构域具有高度的同源性,开发选择性DDRs抑制剂具有极大的挑战。因此,本文在总结DDRs的结构与功能的基础上,基于分子与蛋白的不同结合模式,分4类就已报道的DDRs抑制剂的研究进展进行综述。

As the member of the receptor tyrosine kinase(RTK) superfamily,the discoidin domin receptors(DDRs) kinase was proven to participate in a variety of cellular physiological processes,such as cell proliferation,migration,adhesion and matrix remodeling.Collected evidences certified that abnormal activation of DDRs kinase engaged in the development of many human diseases,including fibrosis,arthritis and cancer.Accordingly,DDRs has been considered as a promising target for diseases treatment.Taken the fact that DDRs have homology with other RTKs,challenges have occurred in the development of selective DDRs inhibitors.In this review,on the basis of the summarization of the structures and function of DDRs,the research progress of four types of DDRs inhibitors were discussed in a medicinal chemistry perspective.■.