Yeung Sai-Ching Jim, Gully Christopher, Lee Mong-Hong
UT M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 079, Houston, Texas 77030, USA.
Mini Rev Med Chem. 2008 Dec;8(14):1514-25. doi: 10.2174/138955708786786480.
Cancer cells undergo mitosis frequently, and many mitotic regulators are aberrantly expressed in these cells. Members of the Aurora family of serine/threonine kinases are expressed during mitosis and carry out vital functions in chromosome alignment, segregation and cytokinesis. Here we review the functions of Aurora-B kinases in mitosis and summarize the current literature on Aurora-B kinase inhibitors. In the process of developing these inhibitors as anticancer drugs, the Aurora kinase inhibitors have also helped to advance our understanding of the role of Aurora kinases in mitosis. The mechanism of action and structure-activity relationship of a selective Aurora-B inhibitor are also discussed. The future may see mechanism guided design of chemotherapy combinations that include these cell-cycle phase-specific drugs. The therapeutic potential of Aurora-B inhibitors is promising.
癌细胞频繁进行有丝分裂，许多有丝分裂调节因子在这些细胞中异常表达。丝氨酸/苏氨酸激酶Aurora家族的成员在有丝分裂期间表达，并在染色体排列、分离和胞质分裂中发挥重要作用。在此，我们综述Aurora-B激酶在有丝分裂中的功能，并总结目前关于Aurora-B激酶抑制剂的文献。在将这些抑制剂开发为抗癌药物的过程中，Aurora激酶抑制剂也有助于增进我们对Aurora激酶在有丝分裂中作用的理解。还讨论了一种选择性Aurora-B抑制剂的作用机制和构效关系。未来可能会出现基于机制指导设计的化疗联合方案，其中包括这些细胞周期阶段特异性药物。Aurora-B抑制剂的治疗潜力很有前景。
