激酶小分子抑制剂研究进展

Research progress on small molecule kinase inhibitors

蛋白激酶与肿瘤、炎症、自身免疫病、神经性疾病等众多疾病的发病机制密切相关,近30年以来激酶作为一个非常有潜力的药物靶点受到了广泛研究。截止2020年4月,FDA批准了59个激酶小分子抑制剂上市,再次激发了针对癌症和其他疾病治疗领域的靶向药物的兴起。本文重点分析了59个已获批上市的药物以及处于Ⅱ期和Ⅲ期临床试验的121个(能检索到分子结构的)激酶小分子抑制剂,按照靶点和适应证等信息进行了汇总和分类分析。此外,本文还简单列举了几类热门靶点及其抑制剂的研究概况。

Protein kinases are intimately involved in the pathogenesis of many diseases such as cancer,inflammation,and autoimmune and neurological diseases.Therefore,kinases have been widely studied as drug targets over the past three decades.As of April,2020,the FDA had approved 59 small molecule kinase inhibitors(SMKIs)in the emerging field of targeted drug therapy.This paper focuses on the biochemistry and pharmacology of these59 SMKIs and 121 SMKIs for which structures can be retrieved and that are now in phaseⅡandⅢclinical trials.In addition,this paper also conducts a simple analysis of several popular targets and their inhibitors.