MEK激酶及其抑制剂的研究进展

The Progress on MEK Kinases and Their Inhibitors

丝裂原活化的细胞外信号调节激酶(mitogen-activated extracellular signal-regulated kinase,MEK)是一种可磷酸化靶蛋白上丝氨酸/苏氨酸和酪氨酸残基的双特异性激酶,也是RASRAF-MEK-ERK信号转导通路的主要组分。该信号通路参与了细胞凋亡,细胞周期进行,细胞迁移、分化、代谢和细胞增殖等众多过程的调节。大量研究表明,MEK结构及其表达水平的改变与肿瘤等多种疾病的发生密切相关。因此,对MEK特异性抑制剂的筛选成了当前国际上关于肿瘤治疗研究的热点。目前,已有多种MEK抑制剂被发现,部分已用于肿瘤等疾病的治疗,并显示出较好的临床疗效。该文将对MEK的结构、功能及MEK抑制剂的临床应用等方面的研究进展作一综述。

The mitogen-activated extracellular and a key component of RAS-RAF-MEK-ERK/MAPK signal-regulated kinase （MEK） is a dual specificity kinase, signaling pathway that phosphorylate serine/threonine and tyrosine residues on target protein. It plays a critical role in the regulation of diverse cellular processes, such as cell proliferation, differentiation, motility and survival, etc. Deregulation of Ras-Raf-MEK-MAPK/ERK pathway occurs in more than 30% of human cancers. As a key node of this pathway, MEK inhibition is an attractive therapeutics strategy in a number of cancers. Several potent, highly selective, non-ATP-competitive MEK inhibitors have been developed and assessed in numerous clinical studies over the past decades. Some of them showed promising therapeutic effects in different types of solid tumors. Here we summarize the advances in MEK structure and function research and discuss the development of MEK inhibitors.