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Aurora kinases regulate cell cycle transit from G2 through cytokinesis and, thus, are targets in cancer therapy.〔Andrews PD, Knatko E, Moore WJ, Swedlow JR. Mitotic mechanics: the auroras come into view. Current Opin in Cell Biol.(2003) 15: pp.672-83〕 There are three mammalian aurora kinase genes, encoding aurora A, B and C. Intense investigation has focused on aurora A and B as they appear to play a role in oncogenesis〔Katayama H., Brinkley WR, Sen S. The Aurora kinases: Role in cell transformation and tumorigenesis. ''Cancer and Metastasis Reviews'' (2003) 22(4): pp.451-64〕 with aurora A identified as a low penetrance tumor susceptibility gene in mice and humans.〔Ewart-Toland A, Briassoului P, de Koning JP et al., Identification of Stk6/STK15 as a candidate low-penetrance tumor susceptibility gene in mouse and human. ''Nature Genetics'' (2003) 34(4): pp.403-12〕 Aurora kinases could be potential targets for novel small-molecule enzyme inhibitors. ==Drug development== A new approach to inhibiting cancer growth that shows great promise for structure-based drug development is targeting enzymes central to cellular mitosis.〔Nigg E.A. Mitotic kinases as regulators of cell division and its checkpoints ''Nat. Rev. Mol. Cell Biol.'' 2:21-32 (2001)〕 Aurora kinases, so named because the scattered mitotic spindles generated by mutant forms resemble the Aurora Borealis, have gained a great deal of attention as possible anticancer drug targets.〔Nicholas Keen & Stephen Taylor, Aurora-kinase inhibitors as anticancer agents. ''Nature Reviews Cancer'' 4, 927-36 (2004)〕〔Richard D. Carvajal, Archie Tse, and Gary K. Schwartz Aurora Kinases: New Targets for Cancer Therapy Clin. Cancer Res., (2006) 12: pp.6869-75.〕 The Aurora enzymes are particularly significant because they are involved in a direct path to the nucleosome by phosphorylating histone H3.〔H Goto, Y Yasui, EA Nigg, and M Inagaki Aurora-B phosphorylates Histone H3 at serine28 with regard to the mitotic chromosome condensation Genes Cells, (2002) 7: pp11-7〕〔Karine Monier, Sandrine Mouradian, and Kevin F. Sullivan DNA methylation promotes Aurora-B-driven phosphorylation of histone H3 in chromosomal subdomain J. Cell Sci., (2007) 120: pp.101-14〕 Furthermore, Aurora kinases are known to be oncogenic and overexpressed in various forms of cancerous growth, including leukemia, colon cancer, prostate cancer〔Edmund Chun Yu Lee et al., Targeting Aurora Kinases for the Treatment of Prostate Cancer. ''Cancer Res.'' (2006) 66: pp.4996-5002.〕 and breast cancer〔Hua Yang et al., Aurora-A Kinase Regulates Telomerase Activity through c-Myc in Human Ovarian and Breast Epithelial Cells ''Cancer Res''. (2004) 64: pp.463-67.〕 tumors.〔Jingyan Fu, Minglei Bian, Qing Jiang, and Chuanmao Zhang Roles of Aurora Kinases in Mitosis and Tumorigenesis Mol. Cancer Res., (2007) 5: pp.1-10.〕 So far three Aurora-kinase inhibitors have been described: ZM447439,〔Bedrick B. Gadea and Joan V. Ruderman: Aurora Kinase Inhibitor ZM447439 Blocks Chromosome-induced Spindle Assembly, the Completion of Chromosome Condensation, and the Establishment of the Spindle Integrity Checkpoint in Xenopus Egg Extracts ''Mol. Biol. Cell'', (2005) 16: pp.1305-18.〕 Hesperadin〔Hauf, S. et al. The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint. ''J. Cell Biol.'' (2003) 161, pp.281–94〕〔Shiho Sakita-Suto et al., Aurora-B Regulates RNA Methyltransferase NSUN2 ''Mol. Biol. Cell'', (2007) 18: pp.1107 17〕 and VX-680. The last is in advanced stages (Phase II clinical trial) of a joint drug development by Vertex Pharmaceuticals's VX-680 (Sausville, 234, last posted on 12/18/06) and Merck & Co.,〔Harrington, E. A. et al. VX-680, a potent and selective small molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. ''Nature Med.'' 10, 262–7 (2004)〕 although the Phase II clinical trial was suspended in November, 2007 due to QT prolongation observed in one patient in Phase I trial. File:ZM-447439.svg|ZM447439 File:Hesperadin.svg|Hesperadin File:VX680.svg|VX-680 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「aurora inhibitor」の詳細全文を読む スポンサード リンク
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