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Hesperadin  

Hesperadin, an inhibitor of human Aurora B, prevented the phosphorylation of substrate with IC(50) of 40 nM. Growth of cultured bloodstream forms was also sensitive to Hesperadin (IC(50) of 50 nM). Hesperadin blocked nuclear division and cytokinesis but not other aspects of the cell cycle. Consequently, growth arrested cells accumulated multiple kinetoplasts, flagella and nucleoli, similar to the effects of RNAi-dependent knockdown of TbAUK1 in cultured bloodstream forms cells. Molecular models predicted high-affinity binding of Hesperadin to both conserved and novel sites in TbAUK1. Collectively, these data demonstrate that cell cycle progression is essential for infections with T. brucei and that parasite Aurora kinases can be targeted with small-molecule inhibitors. [See: Mol Microbiol. 2009 Apr;72(2):442-58. Epub 2009 Mar 6. or http://www.ncbi.nlm.nih.gov/pubmed/19320832] .

 1: Keerthivasan G, Small S, Liu H, Wickrema A, Crispino JD. Vesicle trafficking plays a novel role in erythroblast enucleation. Blood. 2010 Oct 28;116(17):3331-40. Epub 2010 Jul 19. PubMed PMID: 20644112; PubMed Central PMCID: PMC2995360.

2: Hall LL, Byron M, Pageau G, Lawrence JB. AURKB-mediated effects on chromatin regulate binding versus release of XIST RNA to the inactive chromosome. J Cell Biol. 2009 Aug 24;186(4):491-507. PubMed PMID: 19704020; PubMed Central PMCID: PMC2733744.

3: Demidov D, Hesse S, Tewes A, Rutten T, Fuchs J, Ashtiyani RK, Lein S, Fischer A, Reuter G, Houben A. Aurora1 phosphorylation activity on histone H3 and its cross-talk with other post-translational histone modifications in Arabidopsis. Plant J. 2009 Jul;59(2):221-30. PubMed PMID: 19582900.

4: Hivert V, Pierre J, Raingeaud J. Phosphorylation of human enhancer of filamentation (HEF1) on serine 369 induces its proteasomal degradation. Biochem Pharmacol. 2009 Oct 15;78(8):1017-25. Epub 2009 Jun 17. PubMed PMID: 19539609.

5: Jetton N, Rothberg KG, Hubbard JG, Wise J, Li Y, Ball HL, Ruben L. The cell cycle as a therapeutic target against Trypanosoma brucei: Hesperadin inhibits Aurora kinase-1 and blocks mitotic progression in bloodstream forms. Mol Microbiol. 2009 Apr;72(2):442-58. Epub 2009 Mar 6. PubMed PMID: 19320832; PubMed Central PMCID: PMC2697958.

6: Dreier MR, Grabovich AZ, Katusin JD, Taylor WR. Short and long-term tumor cell responses to Aurora kinase inhibitors. Exp Cell Res. 2009 Apr 15;315(7):1085-99. Epub 2009 Feb 20. PubMed PMID: 19233169.

7: Yeh MH, Kao ST, Hung CM, Liu CJ, Lee KH, Yeh CC. Hesperidin inhibited acetaldehyde-induced matrix metalloproteinase-9 gene expression in human hepatocellular carcinoma cells. Toxicol Lett. 2009 Feb 10;184(3):204-10. Epub 2008 Dec 6. PubMed PMID: 19110045.

8: O'Connell CB, Loncarek J, Hergert P, Kourtidis A, Conklin DS, Khodjakov A. The spindle assembly checkpoint is satisfied in the absence of interkinetochore tension during mitosis with unreplicated genomes. J Cell Biol. 2008 Oct 6;183(1):29-36. Epub 2008 Sep 29. PubMed PMID: 18824563; PubMed Central PMCID: PMC2557037.

9: Wang W, Stukenberg PT, Brautigan DL. Phosphatase inhibitor-2 balances protein phosphatase 1 and aurora B kinase for chromosome segregation and cytokinesis in human retinal epithelial cells. Mol Biol Cell. 2008 Nov;19(11):4852-62. Epub 2008 Aug 20. PubMed PMID: 18716057; PubMed Central PMCID: PMC2575180.

10: Kurihara D, Matsunaga S, Uchiyama S, Fukui K. Live cell imaging reveals plant aurora kinase has dual roles during mitosis. Plant Cell Physiol. 2008 Aug;49(8):1256-61. Epub 2008 Jul 1. PubMed PMID: 18593743.

11: Talele TT, McLaughlin ML. Molecular docking/dynamics studies of Aurora A kinase inhibitors. J Mol Graph Model. 2008 Jun;26(8):1213-22. Epub 2007 Nov 17. PubMed PMID: 18096419.

12: Agnese V, Bazan V, Fiorentino FP, Fanale D, Badalamenti G, Colucci G, Adamo V, Santini D, Russo A. The role of Aurora-A inhibitors in cancer therapy. Ann Oncol. 2007 Jun;18 Suppl 6:vi47-52. Review. PubMed PMID: 17591831.

13: Miyauchi K, Zhu X, Foong C, Hosoya H, Murata-Hori M. Aurora B kinase activity is required to prevent polar cortical ingression during cytokinesis. Cell Cycle. 2007 Oct 15;6(20):2549-53. Epub 2007 Jul 31. PubMed PMID: 17726378.

14: McEvoy M, Cao G, Montero Llopis P, Kundel M, Jones K, Hofler C, Shin C, Wells DG. Cytoplasmic polyadenylation element binding protein 1-mediated mRNA translation in Purkinje neurons is required for cerebellar long-term depression and motor coordination. J Neurosci. 2007 Jun 13;27(24):6400-11. PubMed PMID: 17567800.

15: Lipp JJ, Hirota T, Poser I, Peters JM. Aurora B controls the association of condensin I but not condensin II with mitotic chromosomes. J Cell Sci. 2007 Apr 1;120(Pt 7):1245-55. Epub 2007 Mar 13. PubMed PMID: 17356064.

16: Sakita-Suto S, Kanda A, Suzuki F, Sato S, Takata T, Tatsuka M. Aurora-B regulates RNA methyltransferase NSUN2. Mol Biol Cell. 2007 Mar;18(3):1107-17. Epub 2007 Jan 10. PubMed PMID: 17215513; PubMed Central PMCID: PMC1805108.

17: Kurihara D, Matsunaga S, Kawabe A, Fujimoto S, Noda M, Uchiyama S, Fukui K. Aurora kinase is required for chromosome segregation in tobacco BY-2 cells. Plant J. 2006 Nov;48(4):572-80. PubMed PMID: 17087760.

18: Kapoor TM, Lampson MA, Hergert P, Cameron L, Cimini D, Salmon ED, McEwen BF, Khodjakov A. Chromosomes can congress to the metaphase plate before biorientation. Science. 2006 Jan 20;311(5759):388-91. PubMed PMID: 16424343.

19: Kubo M, Matsuda H, Tomohiro N, Harima S. [History and therapeutic evaluation of Citrus hassaku HORT. Tanaka]. Yakushigaku Zasshi. 2004;39(2):363-4. Japanese. PubMed PMID: 16025659.

20: Ladygina NG, Latsis RV, Yen T. [Effect of the pharmacological agent hesperadin on breast and prostate tumor cultured cells]. Biomed Khim. 2005 Mar-Apr;51(2):170-6. Russian. PubMed PMID: 15945350.

21: Yang H, Burke T, Dempsey J, Diaz B, Collins E, Toth J, Beckmann R, Ye X. Mitotic requirement for aurora A kinase is bypassed in the absence of aurora B kinase. FEBS Lett. 2005 Jun 20;579(16):3385-91. PubMed PMID: 15922328.

22: Sessa F, Mapelli M, Ciferri C, Tarricone C, Areces LB, Schneider TR, Stukenberg PT, Musacchio A. Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Mol Cell. 2005 Apr 29;18(3):379-91. PubMed PMID: 15866179.

23: Sumara I, Giménez-Abián JF, Gerlich D, Hirota T, Kraft C, de la Torre C, Ellenberg J, Peters JM. Roles of polo-like kinase 1 in the assembly of functional mitotic spindles. Curr Biol. 2004 Oct 5;14(19):1712-22. PubMed PMID: 15458642.

24: Doggrell SA. Dawn of Aurora kinase inhibitors as anticancer drugs. Expert Opin Investig Drugs. 2004 Sep;13(9):1199-201. Review. PubMed PMID: 15330750.

25: Hauf S, Cole RW, LaTerra S, Zimmer C, Schnapp G, Walter R, Heckel A, van Meel J, Rieder CL, Peters JM. 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 Apr 28;161(2):281-94. Epub 2003 Apr 21. PubMed PMID: 12707311; PubMed Central PMCID: PMC2172906.