Aurora-B kinase inhibitors for cancer chemotherapy.
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.
Yeung
Sai-Ching Jim
SC
UT M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 079, Houston, Texas 77030, USA.
Gully
Christopher
C
Lee
Mong-Hong
MH
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D064107:Aurora Kinase B; D064127:Aurora Kinases; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases