激酶别构调节剂的研究进展

Progress in allosteric modulators of protein kinases

蛋白激酶(protein kinases),即蛋白质磷酸化酶(protein phosphokinases),是一类重要的催化蛋白质磷酸化反应的酶.蛋白激酶活性异常是导致肿瘤发生、生长和转移的重要原因之一.因此,以蛋白激酶作为抗癌靶点,研发新型抗肿瘤药物,己经成为药物研发领域中最重要的研究方向之一,蛋白激酶调节剂也成为颇具潜力的抗肿瘤候选药物.目前已有一个蛋白激酶小分子别构调节剂作为癌症的靶向治疗药物获美国食品药品监督管理局批准上市.与以往的ATP竞争性调节剂相比,蛋白激酶别构抑制剂因选择性好、安全性高、动力学缓慢,而且临床副作用少,已成为现今蛋白激酶抑制剂研发的主要方向.鉴于蛋白激酶别构调节剂在癌症治疗领域展现出的潜在的价值,本文将对蛋白激酶别构调节剂的研究进展进行综述.

Protein kinases are protein phosphokinases that modify other proteins by chemically adding phosphate groups on their residues （phosphorylation）. Aberrant activity of protein kinases usually results in tumor growth and metastasis, and then protein kinases has been one of the most significant research areas in the design and development of novel anticancer drugs. Currently one kinase allosteric drug has been approved by the US Food and Drug Administration. Kinase allosteric drugs possess several distinct advantages over ATP competitive drugs that bind to the same kinases, including higher selectivity, lower toxicity, slow kinetics as well as less side effects. The development of kinase allosteric drugs appears to be a promising new trend in drug discovery. Given the immense advantages of kinase allosteric modulators in cancer therapy, this review focuses on the progress in allosteric modulators of protein kinases.