Pérez de Castro Ignacio, de Cárcer Guillermo, Montoya Guillermo, Malumbres Marcos
Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro 3, Madrid, Spain.
Curr Opin Pharmacol. 2008 Aug;8(4):375-83. doi: 10.1016/j.coph.2008.06.013. Epub 2008 Jul 30.
Among cellular kinases, several cell cycle protein kinases play critical roles in mitotic entry and chromosome segregation. Inhibition of these proteins frequently results in dramatic mitotic arrest and subsequent apoptosis. Most drug discovery efforts have been directed against members of the cyclin-dependent kinase (CDK), Aurora and Polo-like kinase families. Inhibition of these proteins with small molecules has emerged as a powerful research tool and their clinical use is currently being tested in phase I and phase II trials for cancer therapy. New unexplored kinases or new protein domains distinct to the kinase pocket are now being evaluated for the next generation of mitotic drugs. The therapeutic value of inhibiting these kinases will improve with the availability of new specific and potent inhibitors, but it will also rely on a better knowledge of the physiological requirement for these proteins in normal and tumor cell cycles.
在细胞激酶中，几种细胞周期蛋白激酶在有丝分裂启动和染色体分离过程中发挥着关键作用。抑制这些蛋白质通常会导致显著的有丝分裂停滞和随后的细胞凋亡。大多数药物研发工作都针对细胞周期蛋白依赖性激酶（CDK）、极光激酶和Polo样激酶家族的成员。用小分子抑制这些蛋白质已成为一种强大的研究工具，目前其在癌症治疗的I期和II期试验中正在接受临床测试。现在正在评估新一代有丝分裂药物的新的未被探索的激酶或激酶口袋特有的新蛋白质结构域。随着新型特异性和强效抑制剂的出现，抑制这些激酶的治疗价值将会提高，但这也将依赖于对这些蛋白质在正常和肿瘤细胞周期中的生理需求有更深入的了解。
