上市MEK抑制剂Ⅰ期临床试验数据总结

Summary of PhaseⅠdata for MEK inhibitors approved

丝裂原活化的细胞外信号调节激酶(MEK)是选择性磷酸化靶蛋白丝氨酸/苏氨酸和酪氨酸残基的双特异性蛋白激酶,抑制其活性可以阻止细胞增殖和诱导细胞凋亡,故MEK已经成为一个关键的抗癌靶点。抗肿瘤新药Ⅰ期临床试验风险大、致死率高,也是影响药物上市的关键因素之一。目前已有4个MEK抑制剂已被美国食品药品监督管理局(FDA)批准用于癌症治疗,分别为曲美替尼,考比替尼,比美替尼和司美替尼。本文通过对其Ⅰ期临床试验的重要数据进行总结,希望能够对即将开展Ⅰ期临床试验或正在开展临床试验的其他MEK抑制剂提供一些借鉴。

The mitogen-activated extracellular signal-regulated kinase(MEK)is a dual specificity kinase that selectively phosphorylates serine/threonine and tyrosine residues on target protein.MEK has become an attractive target because inhibiting its activity can prevent cell proliferation and induce cell apoptosis.PhaseⅠclinical trials of new anti-tumor drugs have great risk,high fatality rate and is one of the key factors that affect the launch of the drug.Four MEK inhibitors have been approved by the U.S.Food and Drug Administration(FDA),including Trametinib,Cobimetinib,Binimetinib and Selumetinib.In this review,phaseⅠclinical trial data of these drugs are summarized to provide some references for other MEK inhibitors that are going to conduct phaseⅠclinical trials or are in clinical trials.