Novel mitotic targets and their small-molecule inhibitors

Current Cancer Drug Targets

Volumn 7, Issue 8, 2007, Pages 766-784

  Ivachtchenko, Alexandre V ^a   Kiselyov, Alex S ^a   Tkachenko, Sergey E ^a   Ivanenkov, Yan A ^a   Balakin, Konstantin V ^a  

^a CHEMDIV INC   (United States)

Author keywords

Antimitotic agents; Mitotic kinases; Mitotic kinesins; Separase

Indexed keywords

ADOCIASULFATE 2; ANTIMITOTIC AGENT; ARRY 649; AURORA A KINASE; AZD 1152; BI 2536; BIOLOGICAL MARKER; BUB1 RELATED PROTEIN; CENTROMERE PROTEIN E; CHLORPROMAZINE; CHROMOKINESIN; CK 0106023; CYC 116; CYCLIN DEPENDENT KINASE 1; CYCLOPROPANECARBOXYLIC ACID [4 [4 (4 METHYL 1 PIPERAZINYL) 6 (5 METHYL 2H PYRAZOL 3 YLAMINO) 2 PYRIMIDINYLTHIO]PHENYL]AMIDE; DYNEIN ADENOSINE TRIPHOSPHATASE; ENASTROL; ENASTRON; ISPINESIB; JNJ 7706621; KINESIN; M KINESIN; MITOGEN ACTIVATED PROTEIN KINASE; MKC 1260; MKC 1693; MLN 8054; MONASTROL; MP 235; MP 529; N [4 [6 METHOXY 7 (3 MORPHOLINOPROPOXY) 4 QUINAZOLINYLAMINO]PHENYL]BENZAMIDE; ON 01910; PENTAMIDINE; PHA 680632; PHA 739358; POLO LIKE KINASE 1; RABKINESIN 6; RETINOIC ACID; SB 743921; SNS 314; SULFOQUINOVOSYLACYLGLYCEROL DERIVATIVE; TERPENDOLE E; UNCLASSIFIED DRUG; UNINDEXED DRUG; VS 83; VX 528; WORTMANNIN;

ANTINEOPLASTIC ACTIVITY; CLINICAL TRIAL; DRUG MECHANISM; DRUG TARGETING; HUMAN; INHIBITION KINETICS; MITOSIS; MITOSIS INHIBITION; NEOPLASM; NONHUMAN; REVIEW;

ANIMALS; ANTIMITOTIC AGENTS; ANTINEOPLASTIC AGENTS; DRUGS, INVESTIGATIONAL; HUMANS; MICROTUBULES; MITOSIS; NEOPLASMS;

EID: 37449016062     PISSN: 15680096     EISSN: None     Source Type: Journal    
DOI: 10.2174/156800907783220499     Document Type: Review

References (224)

1. Schwartz, G. K.; Shah, M. A. Targeting the Cell Cycle: A New Approach to Cancer Therapy. J. Clin. Oncol. 2005, 23, 9408-9421.
2. Weaver, B. A.; Cleveland, D. W. Decoding the Links Between Mitosis, Cancer, and Chemotherapy: The Mitotic Checkpoint, Adaptation, and Cell Death. Cancer Cell 2005, 8, 7-12.
3. Advait, N.; Wooyoung, H.; Nathanael, G. S. Antimitotic Agents of Natural Origin. Curr. Drug Targets 2006, 7, 305-326.
4. Jordan, M. A.; Wilson, L. Microtubules As a Target for Anticancer Drugs. Nature 2004, 4, 253-265.
5. Miyamoto, D. T.; Perlman, Z. E.; Mitchison, T. G.; Shirasu-Hiza, M. Dynamics of the Mitotic Spindle - potential Therapeutic Targets. Prog. Cell Cycle Res. 2003, 5, 349-360.
6. Wittmann, T.; Hyman, A.; Desai, A. The Spindle: A Dynamic Assembly of Microtubules and Motors. Nat. Cell. Biol. 2001, 3, E28-E34.
7. Mogilner, A.; Wollman, R.; Civelekoglu-Scholey, G.; Scholey, J. Modeling Mitosis. Trends Cell Biol. 2006, 16, 88-96.
8. Karsenti, E.; Vernos, I. The Mitotic Spindle: A Self-made Machine. Science 2001, 294, 543-547.
9. Dustin, P., Ed. Microtubules; 2nd edn, Springer: New York, 1984.
10. Bajer, A. S.; Mole-Bajer, J., Eds. Spindle Dynamics and Chromosome Movements; Academic: New York, 1972.
11. Wood, K. W.; Cornwell, W. D.; Jackson, J. R. The Mitotic Spindle as an Oncology Target. Curr. Opin. Pharmacol. 2001, 1, 370-377.
12. Cavaletti, G.; Cavalletti, E.; Montaguti, P.; Oggioni, N.; De Negri, O.; Tredici, G. Effect on the Peripheral Nervous System of the Short-term Intravenous Administration of Paclitaxel in the Rat. Neurotoxicology 1997, 18, 137-145.
13. Rowinsky, E. K.; Chaudhry, V.; Cornblath, D. R.; Donehower, R. C. Neurotoxicity of Taxol. J. Natl. Cancer Inst. 1993, 15, 107-115.
14. Pitot, H. C.; McElroy, E. A., Jr.; Reid, J. M.; Windebank, A. J.; Sloan, J. A.; Erlichman, C.; Bagniewski, P. G.; Walker, D. L.; Rubin, J.; Goldberg, R. M.; Adjei, A. A.; Ames, M. M. Pharmacological Characterization of Multidrug Resistant MRP-transfected Human Tumor cells. Clin. Cancer Res. 1999, 5, 525-531.
15. Cole, S. P.; Sparks, K. E.; Fraser, K.; Loe, D. W.; Grant, C. E.; Wilson, G. M.; Deeley, R. G. Pharmacological Characterization of Multidrug Resistant MRP-transfected Human Tumor Cells. Cancer Res. 1994, 54, 5902-5910.
16. Lorico, A.; Rappa, G.; Flavell, R. A.; Sartorelli, A. C. Double Knockout of the MRP Gene Leads to Increased Drug Sensitivity In Vitro. Cancer Res. 1996, 56, 5351-5355.
17. Kavallaris, M.; Kuo, D. Y. S.; Burkhart, C. A.; Regl, D. L.; Norris, M. D.; Haber, M.; Horwitz, S. B. Taxol-resistant Epithelial Ovarian Tumors are Associated With Altered Expression of Specific Beta-tubulin Isotypes. J. Clin. Invest. 1997, 100, 1282-1293.
18. Giannakakou, P.; Sackett, D. L.; Kang, Y. K.; Zhan, Z.; Buters, J. T.; Fojo, T.; Poruchynsky, M. S. Paclitaxel-resistant Human Ovarian Cancer Cells Have Mutant Beta-tubulins that Exhibit Impaired Paclitaxel-driven Polymerization. J. Biol. Chem. 1997, 272, 17118-17125.
19. Duhl, D. M.; Renhowe, P. A. Inhibitors of Kinesin Motor Proteins-research and Clinical Progress. Curr. Opin. Drug Discov. Devel. 2005, 8, 431-436.
20. Warner, S. L.; Gray, P. J.; Von Hoff, D. D. Tubulin-associated Drug Targets: Aurora Kinases, Polo-like Kinases, and Others. Semin. Oncol. 2006, 33, 436-448.
21. Hardwick, K. G. The Spindle Checkpoint. Trends Genet. 1998, 14, 1-4.
22. Titu, M. A.; Gilbert, S. P. The Diversity of Molecular Motors: An Overview. Cell Mol. Life Sci. 1999, 56, 181-183.
23. Yildiz, A.; Forkey, J. N.; McKinney, S. A.; Ha, T.; Goldman, Y. E.; Selvin, P. R. Myosin V Walks Hand-over-hand: Single Fluorophore Imaging With 1.5-nm Localization. Science 2003, 300, 2061-2065.
24. Rice, S.; Lin, A. W. A Structural Change in the Kinesin Motor Protein that Drives Motility. Nature 1999, 402, 778-784.
25. Vale, R. D.; Fletterick, R. J. The Design Plan of Kinesin Motors. Annu. Rev. Cell Dev. Biol. 1997, 13, 745-777.
26. Holzbaur, E. L.; Vallee, R. B. Dyneins: Molecular Structure and Cellular Function. Annu. Rev. Cell Biol. 1994, 10, 339-372.
27. Wozniak, M. J.; Milner, R.; Allan, V. N-terminal Kinesins: Many and Various. Traffic 2004, 5, 400-410.
28. Yildiz, A.; Selvin, P. R. Kinesin: Walking, Crawling or Sliding Along? Trends Cell Biol. 2005, 15, 112 -120.
29. Moore, A.; Wordeman, L. The Mechanism, Function and Regulation of Depolymerizing Kinesins During Mitosis. Trends Cell Biol. 2004, 14, 537-546.
30. Hirokawa, N.; Takemura, R. Kinesin Superfamily Proteins and Their Various Functions and Dynamics. Exp. Cell Res. 2004, 301, 50-59.
31. Sablin, E. P. Kinesins and Microtubules: Their Structures and Motor Mechanisms. Curr. Opin. Cell Biol. 2000, 12, 35-41.
32. Kasprzak, A. A.; Hajdo, L. Directionality of Kinesin Motors. Acta Biochim. Pol. 2002, 49, 813-821.
33. Marx, A.; Muller, J.; Mandelkow, E. The Structure of Microtubule Motor Proteins. Adv. Protein Chem. 2005, 71, 299-344.
34. Vale, R. D.; Milligan, R. A. The Way Things Move: Looking Under The Hood of Molecular Motor Proteins. Science 2000, 288, 88-95.
35. Miki, H.; Setou, M.; Kaneshiro, K.; Hirokawa, N. All kinesin superfamily protein, KIF, genes in mouse and human. Proc. Natl. Acad. Sci. USA 2001, 98, 7004-7011.
36. Goldstein, L. S.; Philp, A. V. The Road Less Traveled: Emerging Principles of Kinesin Motor Utilization. Annu. Rev. Cell Dev. Biol. 1999, 15, 141-183.
37. Kozielski, F.; Sack, S.; Marx, A.; Thormahlen, M.; Schonbrunn, E.; Biou, V.; Thompson, A.; Mandelkow, E. M.; Mandelkow, E. The Crystal Structure of Dimeric Kinesin and Iplications for Microtubule-dependent Motility. Cell 1997, 91, 985-994.
38. Hua, W.; Chung, J.; Gelles, J. Distinguishing Inchworm and Hand-Over-Hand Processive Kinesin Movement by Neck Rotation Measurements. Science 2002, 295, 844-848.
39. Hoenger, A.; Thormahlen, M.; Diaz-Avalos, R.; Doerhoefer, M.; Goldie, K. N.; Muller, J.; Mandelkow, E. A New Look at the Microtubule Binding Patterns of Dimeric Kinesins. J. Mol. Biol. 2000, 297, 1087-1103.
40. Yildiz, A.; Tomishige, M.; Vale, R. D.; Selvin, P. R. Kinesin Walks Hand-Over-Hand. Science 2004, 303, 676-678.
41. Hildebrandt, E. R.; Hoyt, M. A. Mitotic Motors in Saccharomyces Cerevisiae. Biochim. Biophys. Acta 2000, 1496, 99-116.
42. Goshima, G.; Vale, R. D. The Roles of Microtubule-based Motor Proteins in Mitosis: Comprehensive RNAi Analysis in the Drosophila S2 Cell Line. J. Cell Biol. 2003, 162, 1003-1016.
43. Enos, A. P.; Morris, N. R. Mutation of a Gene that Encodes a Kinesin-like Protein Blocks Nuclear Division in A. nidulans. Cell 1990, 60, 1019-1027.
44. Meluh, P. B.; Rose, M. D. KAR3, a Kinesin-related Gene Required for Yeast Nuclear Fusion. Cell 1990, 60, 1029-1041.
45. Wickstead, B.; Gull, K. A "Holistic" Kinesin Phylogeny Reveals New Kinesin Families and Predicts Protein Functions. Mol. Biol. Cell 2006, 17, 1734-1743.
46. Lawrence, C. J.; Dawe, R. K.; Christie, K. R.; Cleveland, D. W.; Dawson, S. C.; Endow, S. A.; Goldstein, L. S.; Goodson, H. V.; Hirokawa, N.; Howard, J.; Malmberg, R. L.; McIntosh, J. R.; Miki, H.; Mitchison, T. J.; Okada, Y.; Reddy, A. S.; Saxton, W. M.; Schliwa, M.; Scholey, J. M.; Vale, R. D.; Walczak, C. E.; Wordeman, L. A Standardized Kinesin Nomenclature. J. Cell. Biol. 2004, 167, 19-22.
47. Dagenbach, E. M.; Endow, S. A. A New Kinesin Tree. J. Cell. Sci. 2004, 117, 3-7.
48. Zhu, G.; Zhao, J.; Bibikova, M.; Leverson, J. D.; Bossy-Wetzel, E.; Fan, J.-B.; Abraham, R. T.; Jiang, W. Functional Analysis of Human Microtubulebased Motor Proteins, the Kinesins and Dyneins, in Mitosis/Cytokinesis Using RNA Interference. Mol. Biol. Cell 2005, 16, 3187-3199.
49. Sarli, V.; Giannis, A. Inhibitors of Mitotic Kinesins: Next-Generation Antimitotics. J. Med. Chem. 2006, 1, 293-298.
50. Wordeman, L.; Wagenbach, M.; Maney, T. Mutations in the ATP-binding domain affect the subcellular distribution of mitotic centromere-associated kinesin (MCAK). Cell Biol. Int. 1999, 23, 275-286.
51. Helenius, J.; Brouhard, G.; Kalaidzidis, Y.; Diez, S.; Howard, J. The Depolymerizing Kinesin MCAK Uses Lattice Diffusion to Rapidly Target Microtubule Ends. Nature 2006, 441, 115-119.
52. Chen, M. C.; Zhou, Y.; Detrich, H. W., 3rd. Zebrafish Mitotic Kinesin-like Protein 1 (Mklp1) Functions in Embryonic Cytokinesis. Physiol. Genomics 2002, 8, 51-66.
53. Whitehead, C. M.; Rattner, J. B. Expanding the Role of HsEg5 Within the Mitotic and Post-mitotic Phases of the Cell Cycle. J. Cell Sci. 1998, 111, 2551-2561.
54. Sharp, D. J.; Yu, K. R.; Sisson, J. C.; Sullivan, W.; Scholey, J. M. Antagonistic Microtubule-sliding Motors Position Mitotic Centrosomes in Drosophila Early Embryos. Nature Cell Biol. 1999, 1, 51-54.
55. Sawin, K. E.; LeGuellec, K.; Philippe, M.; Mitchison, T. J. Mitotic Spindle Organization by a Plus-end-directed Microtubule Motor. Nature 1992, 359, 540-543.
56. Blangy, A.; Lane, H. A.; d'Herin, P.; Harper, M.; Kress, M.; Nigg, E. A. Phosphorylation by p34cdc2 Regulates Spindle Association of Human Eg5, a Kinesin-related Motor Essential for Bipolar Spindle Formation In Vivo Cell 1995, 83, 1159-1169.
57. Kashina, A. S.; Baskin, R. J.; Cole, D. G.; Wedman, K. P.; Saxton, W. M.; Scholey, J. M. A Bipolar Kinesin. Nature 1996, 379, 270- 272.
58. Turner, J.; Anderson, R.; Guo, J.; Beraud, C.; Fletterick, R.; Sakowicz, R. Crystal Structure of the Mitotic Spindle Kinesin Eg5 Reveals a Novel Conformation of the Neck-linker. J. Biol. Chem. 2001, 276, 25496-25502.
59. Kapoor, T. M.; Mitchison, T. J. Eg5 is Static in Bipolar Spindles Relative to Tubulin: Evidence for a Static Spindle Matrix. J. Cell Biol. 2001, 154, 1125-1133.
60. Cochran, J. C.; Sontag, C. A.; Maliga, Z.; Kapoor, T. M.; Correia, J. J.; Gilbert, S. P. Mechanistic Analysis of the Mitotic Kinesin Eg5. J. Biol. Chem. 2004, 279, 38861-38870.
61. Mayer, T. U.; Kapoor, T. M.; Haggarty, S. J.; King, R. W.; Schreiber, S. L.; Mitchison, T. J. Small Molecule Inhibitor of Mitotic Spindle Bipolarity Identified in a Phenotype-based Screen. Science 1999, 286, 971-974.
62. Davis, D. A.; Sarkar, S. H.; Hussain, M.; Li, Y.; Sarkar, F. H. Increased Therapeutic Potential of an Experimental Anti-mitotic Inhibitor SB715992 by Genistein in PC-3 Human Prostate Cancer Cell Line. BMC Cancer 2006, 6, 22.
63. Cheng, J.; Qidong, Y.; Zhiyu, Li.; Qinglong, G. Kinesin Spindle Protein Inhibitors as Anticancer Agents. Expert Opin. Ther. Patents 2006, 16, 1517-1532.
64. Vijapurkar, U.; Wang, W.; Herbst, R. Potentiation of Kinesin Spindle Protein Inhibitor-induced Cell Death by Modulation of Mitochondrial and Death Receptor Apoptotic Pathways. Cancer Res. 2007, 67, 237-245.
65. Desai, A.; Verma, S.; Mitchison, T. J.; Walczak, C. E. Kin I Kinesins Are Microtubule-destabilizing Enzymes. Cell 1999, 96, 69-78.
66. Moores, C. A.; Yu, M.; Guo, J.; Beraud, C.; Sakowicz, R.; Milligan, R. A. A Mechanism for Microtubule Depolymerization by Kin I Kinesins. Mol. Cell 2002, 9, 903-909.
67. Hunter, A. W.; Caplow, M.; Coy, D. L.; Hancock, W. O.; Diez, S.; Wordeman, L.; Howard, J. The Kin I kinesin MCAK is a Microtubule Depolymerase that Forms an ATP-hydrolyzing Complex at Microtubule Ends. Mol. Cell 2003, 11, 445-457.
68. Maney, T.; Hunter, A. W.; Wagenbach, M.; Wordeman, L. Mitotic Centromere-associated Kinesin is Important for Anaphase Chromosome Segregation. J. Cell Biol. 1998, 142, 787-801.
69. Maney, T.; Wagenbach, M.; Wordeman, L. Molecular Dissection of The Microtubule Depolymerizing Activity of Mitotic Centromere-associated Kinesin. J. Biol. Chem. 2001, 276, 34753-34758.
70. Kline-Smith, S. L.; Walczak, C. E. Mitotic Spindle Asembly and Chromosome Segregation: Refocusing on Microtubule Dynamics. Mol. Cell 2004, 15, 317-327.
71. Rogers, G. C.; Rogers, S. L.; Schwimmer, T. A.; Ems-McClung, S. C.; Walczak, C. E.; Vale, R. D.; Scholey, J. M.; Sharp, D. J. Two Mitotic Kinesins Cooperate to Drive Sister Chromatid Separation During Anaphase. Nature 2004, 427, 364-370.
72. Gaetz, J.; Kapoor, T. M. Dynein/dynactin Regulate Metaphase Spindle Length by Targeting Depolymerizing Activities to Spindle Poles. J. Cell Biol. 2004, 166, 465-471.
73. Ganem, N. J.; Compton, D. A. The Kin I Kinesin Kif2a is Required for Bipolar Spindle Assembly Through a Functional Relationship With MCAK. J. Cell Biol. 2004, 166, 473-478.
74. Walczak, C.; Gan, E. C.; Desai, A.; Mitchison, T. J.; Kline-Smith, S. L. The Microtubule-destabilizing Kinesin, XKCM1 is Required for Chromosome Positioning During Spindle Assembly. Curr. Biol. 2002, 12, 1885-1889.
75. Ovechkina, Y.; Wagenbach, M.; Wordeman, L. K-loop Insertion Restores Microtubule Depolymerizing Activity of a "Neckless" MCAK Mutant. J. Cell Biol. 2004, 159, 557-562.
76. Ogawa, T.; Nitta, R.; Okada, Y.; Hirokawa, N. A Common Mechanism for Microtubule Destabilizers M-Type Kinesins Stabilize Curling of The Protofilament Using the Class-specific Neck and Loops. Cell 2004, 116, 591-602.
77. Moore, A.; Wordeman, L. C-terminus of Mitotic Centromere- associated Kinesin (MCAK) Inhibits its Lattice-stimulated ATPase Activity. Biochem. J. 2004, 383, 227-235.
78. Moores, C. A.; Cooper, J.; Wagenbach, M.; Ovechkina, Y.; Wordeman, L.; Milligan, R. A. The Role of the Kinesin-13 Neck in Microtubule Depolymerization. Cell Cycle 2006, 5, 1812-1815.
79. Ayana, T.; Moore, K. E. Rankin, G. von D.; Peris, L.; Wagenbach, M.; Ovechkina, Y.; Andrieux, A.; Job, D.; Wordeman. L. MCAK Associates With the Tips of Polymerizing Microtubules. J. Cell Biol. 2005, 169, 391-397.
80. Walczak, C. E.; Mitchison, T. J.; Desai, A. XKCM1, a Xenopus Kinesin-related Protein that Regulates Microtubule Dynamics During Mitotic Spindle Assembly. Cell 1996, 84, 37-47.
81. Mennella, V.; Rogers, G. C.; Rogers, S. L.; Buster, D. W.; Vale, R. D.; Sharp, D. J. Functionally Distinct Kinesin-13 Family Members Cooperate to Regulate Microtubule Dynamics During Interphase. Nat. Cell Biol. 2005, 7, 235-245.
82. Niederstrasser, H.; Salehi-Had, H.; Gan, E. C.; Walczak, C.; Nogales, E. XKCM1 Acts on a Single Protofilament and Requires the C-terminus of Tubulin. J. Mol. Biol. 2002, 316, 817-828.
83. Yen, T. J.; Li, G.; Schaar, B. T.; Szilak, I.; Cleveland, D. W. CENP-E is a Putative Kinetochore Motor that Accumulates Just Before Mitosis. Nature 1992, 359, 536-539.
84. Wood, K. W.; Sakowicz, R.; Goldstein, L. S.; Cleveland, D. W. CENP-E is a Plus End-directed Kinetochore Motor Required for Metaphase Chromosome Alignment. Cell 1997, 91, 357-366.
85. Lombillo, V. A.; Nislow, C.; Yen, T. J.; Gelfand, V. I.; McIntosh, J. R. Antibodies to the Kinesin Motor Domain and CENP-E Inhibit Microtubule Depolymerization-dependent Motion of Chromosomes In Vitro. J. Cell Biol. 1995, 128, 107-115.
86. Grancell, A.; Sorger, P. K. Chromosome Movement: Kinetochores Motor Along. Curr. Biol. 1998, 8, R382-R385.
87. Neumann, E.; Garcia-Saez, I.; Debonis, S.; Wade, R. H.; Kozielski, F.; Conway, J. F. Human Kinetochore-associated Kinesin CENP-E Visualized at 17 A Resolution Bound to Microtubules. J. Mol. Biol. 2006, 362, 203-211.
88. Yao, X.; Abrieu, A.; Zheng, Y.; Sullivan, K. F.; Cleveland, D. W. CENP-E Forms a Link Between Attachment of Spindle Microtubules to Kinetochores and the Mitotic Checkpoint. Nat. Cell. Biol. 2000, 2, 484-491.
89. Yen, T. J.; Compton, D. A.; Wise, D.; Zinkowski, R. P.; Brinkley, B. R.; Earnshaw, W. C.; Cleveland, D. W. EMBO J. 1991, 10, 1245-1254.
90. McEwen, B. F.; Chan, G. K.; Zubrowski, B.; Savoian, M. S.; Sauer, M. T.; Yen, T. CENP-E is Essential for Reliable Bioriented Spindle Attachment, but Chromosome Alignment Can be Achieved Via Redundant Mechanisms in Mammalian Cells. J. Mol. Biol. Cell 2001, 12, 2776-2789.
91. Abrieu, A.; Kahana, J. A.; Wood, K. W.; Cleveland, D. W. CENP-E as an Essential Component of the Mitotic Checkpoint In Vitro. Cell 2000, 102, 817-826.
92. Liao, H.; Li, G.; Yen, T. J. Mitotic Regulation of the Microtubule Crosslinking Activity of CENP-E Kinetochore Protein. Science 1994, 265, 394-398.
93. Zhu, C.; Jiang, E. Cell Cycle-dependent Translocation of PRC1 on the Spindle by Kif4 is Essential for Midzone Formation and Cytokinesis. Proc. Natl. Acad. Sci. USA 2005, 102, 343-348.
94. Zhu, C.; Bossy-Wetzel, E.; Jiang, W. Recruitment of MKLP1 to the Spindle Midzone/midbody by INCENP is Essential for Midbody Formation and Completion of Cytokinesis in Human Cells. Biochem. J. 2005, 389, 373-381.
95. Gruneberg, U.; Neef, R.; Honda, R.; Nigg, E. A.; Barr, F. A. Relocation of Aurora B From Centromeres to the Central Spindle at the Metaphase to Anaphase Transition Requires MKlp2. J. Cell Biol. 2004, 166, 167-172.
96. Fontijn, R. D.; Goud, B.; Echard, A.; Jollivet, F.; van Marle, J.; Pannekoek, H.; Horrevoets, A. J. The Human Kinesin-like Protein RB6K is Under Tight Cell Cycle Control and is Essential for Cytokinesis. Mol. Cell Biol. 2001, 21, 2944-2955.
97. Abaza, A.; Soleilhac, J. M.; Westendorf, J. M.; Piel, M.; Crevel, I.; Roux, A.; Pirollet, F. M Phase Phosphoprotein 1 is a Human Plus-enddirected Kinesinrelated Protein Required for Cytokinesis. J. Biol. Chem. 2003, 278, 27844-27852.
98. Echard, A.; Jollivet, F.; Martinez, O.; Lacapere, J. J.; Rousselet, A.; Janoueix- Lerosey, I.; Goud, B. Interaction of a Golgi-associated Kinesinlike Protein With Rab6. Science 1998, 279, 580-585.
99. Neef, R.; Preisinger, C.; Sutcliffe, J.; Kopajtich, R.; Nigg, E. A.; Mayer, T. U.; Barr, F. A. Phosphorylation of Mitotic Kinesin-like Protein 2 by Pololike Kinase 1 is Required for Cytokinesis. J. Cell Biol. 2003, 162, 863-875.
100. Kuriyama, R.; Gustus, C.; Terada, Y.; Uetake, Y.; Matuliene, J. CHO1, a Mammalian Kinesin-like Protein, Interacts With F-actin and is Involved in the Terminal Phase of Cytokinesis. J. Cell Biol. 2002, 156, 783-790.
101. Nislow, C.; Lombillo, V. A.; Kuriyama, R.; McIntosh, J. R. A Plus-end-directed Motor Enzyme that Moves Antiparallel Microtubules In Vitro Localizes to the Interzone of Mitotic Spindles. Nature 1992, 359, 543-547.
102. Wright, B. D.; Terasaki, M.; Scholey, J. M. Roles of Kinesin and Kinesinlike Proteins in Sea Urchin Embryonic Cell Division: Evaluation Using Antibody Microinjection. J. Cell Biol. 1993, 123, 681-689.
103. Yu, W.; Cook, C.; Sauter, C.; Kuriyama, R.; Kaplan, P. L.; Baas, P. W. Depletion of a Microtubule-Associated Motor Protein Induces the Loss of Dendritic Identity. J. Neurosci. 2000, 20, 5782-5791.
104. Mountain, V.; Simerly, C.; Howard, L.; Ando, A.; Schatten, G.; Compton, D. A. J. The Kinesin-related Protein, HSET, Opposes the Activity of Eg5 and Cross-links Microtubules in the Mammalian Mitotic Spindle. Cell Biol. 1999, 147, 351-366.
105. Gottesman, M. M.; Fojo, T.; Bates, S. E. Multidrug Resistance in Cancer: Role of ATP-Dependent Transporters. Nat. Rev. Cancer 2002, 2, 48-58.
106. Sakowicz, R.; Berdelis, M. S.; Ray, K.; Blackburn, C. L.; Hopmann, C.; Faulkner, D. J.; Goldstein, L. S. A Marine Natural Product Inhibitor of Kinesin Motors. Science 1998, 280, 292-295.
107. Garbaccio, R. M.; Fraley, M. E.; Tasber, E. S.; Olson, C. M.; Hoffman, W. F.; Arrington, K. L.; Torrent, M.; Buser, C. A.; Walsh, E. S.; Hamilton, K.; Schaber, M. D.; Fernandes, C.; Lobell, R. B.; Tao, W.; South, V. J.; Yan, Y.; Kuo, L. C.; Prueksaritanont, T.; Slaughter, D. E.; Shu, C.; Heimbrook, D. C.; Kohl, N. E.; Huber, H. E.; Hartman, G. D. Kinesin Spindle Protein (KSP) Inhibitors. Part 3: Synthesis and Evaluation of Phenolic 2,4-Diaryl-2,5- dihydropyrroles With Reduced hERG Binding and Employment of a Phosphate Prodrug Strategy for Aqueous Solubility. Bioorg. Med. Chem. Lett. 2006, 16, 1780-1787.
108. Cox, C. D.; Breslin, M. J.; Whitman, D. B.; Coleman, P. J.; Garbaccio, R. M.; Fraley, M. E.; Zrada, M. M.; Buser, C. A.; Walsh, E. S.; Hamilton, K.; Lobell, R. B.; Tao, W.; Abrams, M. T.; South, V. J.; Huber, H. E.; Kohl, N. E.; Hartman, G. D. Kinesin Spindle Protein (KSP) Inhibitors. Part V: Discovery of 2-Propylamino-2,4-diaryl-2,5-dihydropyrroles as Potent, Water-soluble KSP Inhibitors, and Modulation of Their Basicity by Betafluorination to Overcome Cellular Efflux by P-glycoprotein. Bioorg. Med. Chem. Lett. 2007, 17, 2697-2702.
109. Fraley, M. E.; Garbaccio, R. M.; Arrington, K. L.; Hoffman, W. F.; Tasber, E. S.; Coleman, P. J.; Buser, C. A.; Walsh, E. S.; Hamilton, K.; Fernandes, C.; Schaber, M. D.; Lobell, R. B.; Tao, W.; South, V. J.; Yan, Y.; Kuo, L. C.; Prueksaritanont, T.; Shu, C.; Torrent, M.; Heimbrook, D. C.; Kohl, N. E.; Huber, H. E.; Hartman, G. D. Kinesin Spindle Protein (KSP) Inhibitors. Part 2: The Design, Synthesis, and Characterization of 2,4-Diaryl-2,5- dihydropyrrole Inhibitors of the Mitotic Kinesin KSP. Bioorg. Med. Chem. Lett. 2006, 16, 1775-1779.
110. Miglarese, M. R.; Carlson, R. O. Development of New Cancer Therapeutic Agents Targeting Mitosis. Exp. Opin. Invest. Drugs 2006, 15, 1411-1425.
111. Tao, W.; South, V.; Sepp-Lorenzino, L.; Lobell, R. The Induction of Apoptosis by a KSP Inhibitor is Independent of p53. Proc. Am. Assoc. Cancer Res. (AACR) 2006, 47, 2065-2072.
112. Tao, W.; South, V. J.; Zhang, Y.; Davide, J. P.; Farrell, L.; Kohl, N. E.; Sepp-Lorenzino, L.; Lobell, R. B. Induction of Apoptosis by an Inhibitor of the Mitotic Kinesin KSP Requires Both Activation of the Spindle Assembly Checkpoint and Mitotic Slippage. Cancer Cell 2005, 8, 49-59.
113. Cox, C. D.; Torrent, M.; Breslin, M. J.; Mariano, B. J.; Whitman, D. B.; Coleman, P. J.; Buser, C. A.; Walsh, E. S.; Hamilton, K.; Schaber, M. D.; Lobell, R. B.; Tao, W.; South, V. J.; Kohl, N. E.; Yan, Y.; Kuo, L. C.; Prueksaritanont, T.; Slaughter, D. E.; Li, C.; Mahan, E.; Lu, B.; Hartman, G. D. Kinesin Spindle Protein (KSP) Inhibitors. Part 4: Structure-based Design of 5-Alkylamino-3,5-diaryl-4,5-dihydropyrazoles as Potent, Water-soluble Inhibitors of the Mitotic Kinesin KSP. Bioorg. Med. Chem. Lett. 2006, 16, 3175-3179.
114. Kaiser, A.; Brembeck, F. H.; Nicke, B.; Wiedenmann, B.; Riecken, E. O.; Rosewicz, S. All-trans-retinoic Acid-mediated Growth Inhibition Involves Inhibition of Human Kinesin-related Protein HsEg5. J. Biol. Chem. 1999, 274, 18925-18931.
115. Nakazawa, J.; Yajima, J.; Usui, T.; Ueki, M.; Takatsuki, A.; Imoto, M.; Toyoshima, Y. Y.; Osada, H. A Novel Action of Terpendole E on the Motor Activity of Mitotic Kinesin Eg5. Chem. Biol. 2003, 10, 131-137.
116. Hotha, S.; Yarrow, J. C.; Yang, J. G.; Garrett, S.; Renduchintala, V.; Mayer, T. U.; Kapoor, T. M. HR22C16: A Potent Small Molecule Probe for the Dynamics of Cell Division. Angew. Chem. Int. Ed. Engl. 2003, 42, 2379-2382.
117. Bergnes, G.; Ha, E.; Feng, B.; Smith, W. W.; Yao, B.; Tochimoto, T.; Lewis, E. R.; Lee, Y.; Moody, R. S.; Finer, J. T.; Turincio, A.; Wood, K. W.; Sakowicz, R.; Crompton, A. M.; Chabala, J. C.; Sakowicz, R.; Finer, J. T.; Beraud, C.; Crompton, A.; Lewis, E.; Fritsch, A.; Lee, Y.; Mak, J.; Moody, R.; Turincio, R.; Chabala, J. C.; Gonzales, P.; Roth, S.; Weitman, S.; Wood, K. W. Anti-tumour Activity of a Kinesin Inhibitor. Cancer Res. 2004, 64, 3276-3280.
118. Jiang, C.; Chen, Y.; Wang, X.; You, Q. Docking Studies on Kinesin Spindle Protein Inhibitors: an Important Cooperative 'Minor Binding Pocket' which Increases the Binding Affinity Significantly. J. Mol. Model. 2007, 13, 987-992.
119. Quasthoff, S.; Hartung, H. P. Chemotherapy-induced Peripheral Neuropathy. J. Neurol. 2002, 249, 9-17.
120. Gartner, M.; Sunder-Plassmann, N.; Seiler, J.; Utz, M.; Vernos, I.; Surrey, T.; Giannis, A. Development and Biological Evaluation of Potent and Specific Inhibitors of Mitotic Kinesin Eg5. Chembiochem 2005, 6, 1173-1177.
121. Maliga, Z.; Kapoor, T. M.; Mitchison, T. J. Evidence that Monastrol is an Allosteric Inhibitor of the Mitotic Kinesin Eg5. Chem. Biol. 2002, 9, 989-996.
122. Sarli, V.; Huemmer, S.; Sunder-Plassmann, N.; Mayer, T. U.; Giannis, A. Synthesis and Biological Evaluation of Novel Eg5 Inhibitors. Chembiochem 2005, 6, 2005-2013.
123. Sahara, H.; Ishikawa, M.; Takahashi, N.; Ohtani, S.; Sato, N.; Gasa, S.; Akino, T.; Kikuchi, K. In Vivo Anti-tumour Effect of 3-Sulphonoquinovosyl 1′-Monoacylglyceride Isolated From Sea Urchin (Strongylocentrotus intermedius) Intestine. Br. J. Cancer 1997, 75, 324-332.
124. Mizushina, Y.; Kasai, N.; Iijima, H.; Sugawara, F.; Yoshida, H.; Sakaguchi, K. Sulfo-quinovosyl-acyl-glycerol (SQAG), a Eukaryotic DNA Polymerase Inhibitor and Anti-cancer Agent. Curr. Med. Chem. Anticancer Agents 2005, 5, 613-25.
125. Aoki, S.; Ohta, K.; Yamazaki, Y.; Sugawara, F.; Sakaguchi, K. Mammalian Mitotic Centromere-associated Kinesin (MCAK). A New Molecular Target of Sulfoquinovosylacylglycerols Novel Antitumor and Immunosuppressive Agents. FEBS Lett. 2005, 272, 2132-2140.
126. Shima, H.; Tsuruma, T.; Sahara, H.; Takenouchi, M.; Takahashi, N.; Iwayama, Y.; Yagihashi, A.; Watanabe, N.; Sato, N.; Hirata, K. Treatment with beta-SQAG9 Prevents Rat Hepatic Ischemia-reperfusion Injury. Transplant. Proc. 2005, 37, 417-421.
127. McDonald, A.; Bergnes, G.; Morgans, D. J., Jr. Preparation of Quinazolinediones as Kif15 Kinesin Inhibitors for Treating Cellular Proliferative Disorders. US Patent: 20040053948, 2004.
128. Scolnick, D. M.; Halazonetis, T. D. Chfr Defines a Mitotic Stress Checkpoint that Delays Entry Into Metaphase. Nature 2000, 406, 430-435.
129. Brady, D. M.; Hardwick, K. G. Complex Formation Between Mad1p, Bub1p and Bub3p is Crucial for Spindle Checkpoint Function. Curr. Biol. 2000, 10, 675-678.
130. Nigg, E. A. Mitotic Kinases as Regulators of Cell Division and its Checkpoints. Nat. Rev. Mol. Cell. Biol. 2001, 2, 21-32.
131. Bischoff, J. R.; Plowman, G. D. The Aurora/Ipl1p Kinase Family: Regulators of Chromosome Segregation and Cytokinesis. Trends Cell Biol. 1999, 9, 454-459.
132. Elledge, S. J. Cell Cycle Checkpoints: Preventing an Identity Crisis. Science 1996, 274, 1664-1672.
133. Burke, D. J. Complexity in the Spindle Checkpoint. Curr. Opin. Genet. Dev. 2000, 10, 26-31.
134. Tao, W. The Mitotic Checkpoint in Cancer Therapy. Cell Cycle 2005, 4, 1495-1499.
135. Kokkinakis, D. M.; Brickner, A. G.; Kirkwood, J. M.; Liu, X.; Goldwasser, J. E.; Kastrama, A.; Sander, C.; Bocangel, D.; Chada, S. Mitotic Arrest, Apoptosis, and Sensitization to Chemotherapy of Melanomas by Methionine Deprivation Stress. Mol. Cancer Res. 2006, 4, 575-589.
136. Russell, P. Checkpoints on the Road to Mitosis. Trends Biochem. Sci. 1998, 23, 399-402.
137. Kumagai, A.; Dunphy, W. G. Purification and Molecular Cloning of Plx1, a Cdc25-Regulatory Kinase From Xenopus Egg Extracts. Science 1996, 273, 1377-1380.
138. Smits, V. A.; Klompmaker, R.; Arnaud, L.; Rijksen, G.; Nigg, E. A.; Medema, R. H. Polo-like Kinase-1 is a Target of the DNA Damage Checkpoint. Nature Cell Biol. 2000, 2, 672-676.
139. Sanchez, Y.; Bachant, J.; Wang, H.; Hu, F.; Liu, D.; Tetzlaff, M.; Elledge, S. J. Control of the DNA Damage Checkpoint by Chk1 and Rad53 Protein Kinases Through Distinct Mechanisms. Science 1999, 286, 1166-1171.
140. Nigg, E. A. Cyclin-dependent Protein Kinases: Key Regulators of the Eukaryotic Cell Cycle. BioEssays 1995, 17, 471-480.
141. Van Hooser, A. A.; Mancini, M. A.; Allis, C. D.; Sullivan, K. F.; Brinkley, B. R. The Mammalian Centromere: Structural Domains and the Attenuation of Chromatin Modeling. FASEB J. 1999, 13, S216-S220.
142. Fry, A. M.; Yamano, H. APC/C-mediated Degradation in Early Mitosis: How to Avoid Spindle Assembly Checkpoint Inhibition. Cell Cycle 2006, 5, 1487-1491.
143. Chan, G. K.; Yen, T. J. The Mitotic Checkpoint: A Signaling Pathway that Allows a Single Unattached Kinetochore to Inhibit Mitotic Exit. Prog. Cell. Cycle Res. 2003, 5, 431-439.
144. Beth, A. A.; Cleveland, W.; Cleveland, D .W. Decoding the Links Between Mitosis, Cancer, and Chemotherapy: The Mitotic Checkpoint, Adaptation, and Cell Death. Cancer Cell 2005, 8, 7-12.
145. Chan, G. K.; Liu, S. T.; Yen, T. J. Kinetochore Structure and Function. Trends Cell Biol. 2005, 15, 589-598.
146. Morgan, D. O. Regulation of the APC and the Exit From Mitosis. Nature Cell Biol. 1999, 1, E47-E53.
147. Fang, G. Checkpoint Protein BubR1 Acts Synergistically with Mad2 to Inhibit Anaphase-promoting Complex. Mol. Biol. Cell 2002, 13, 755-766.
148. Jeganathan, K. B.; van Deursen, J. M. Differential Mitotic Checkpoint Protein Requirements in Somatic and Germ Cells. Biochem. Soc. Trans. 2006, 34, 583-586.
149. Habu, T.; Kim, S. H.; Weinstein, J.; Matsumoto, T. Identification of a MAD2-binding Protein, CMT2, and its Role in Mitosis. EMBO J. 2002, 21, 6419-6428.
150. Wasch, R.; Engelbert, D. Anaphase-promoting Complex-dependent Proteolysis of Cell Cycle Regulators and Genomic Instability of Cancer Cells. Oncogene 2005, 24, 1-10.
151. Baker, D. J.; Jeganathan, K. B.; Cameron, J. D.; Thompson, M.; Juneja, S.; Kopecka, A.; Kumar, R.; Jenkins, R. B.; de Groen, P. C.; Roche, P.; van Deursen, J. M. BubR1 Insufficiency Causes Early Onset of Aging-associated Phenotypes and Infertility in Mice. Nat. Genet. 2004, 36, 744-749.
152. Nasmyth, K.; Peters, J. M.; Uhlmann, F. Splitting the Chromosome: Cutting the Ties that Bind Sister Chromatids. Science 2000, 288, 1379-1385.
153. Sumara, I.; Vorlaufer, E.; Gieffers, C.; Peters, B. H.; Peters, J. M. Characterization of Vertebrate Cohesion Complexes and Their Regulation in Prophase. J. Cell Biol. 2000, 151, 749-762.
154. Losada, A.; Yokochi, T.; Kobayashi, R.; Hirano, T. Identification and Characterization of SA/Scc3p Subunits in the Xenopus and Human Cohesin Complexes. J. Cell Biol. 2000, 150, 405-416.
155. Yeh, E.; Skibbens, R. V.; Cheng, J. W.; Salmon, E. D.; Bloom, K. Spindle Dynamics and Cell Cycle Regulation of Dynein in the Budding Yeast, Saccharomyces Cerevisiae. J. Cell Biol. 1995, 130, 687-700.
156. Chad, G.; Bloom, P.; Bloom, K. Dynamic Microtubules Lead the Way for Spindle Positioning. Nature 2004, 5, 481-492.
157. Fraschini, R.; D'Ambrosio, C.; Venturetti, M.; Lucchini, G.; Piatti, S. Disappearance of the Budding Yeast Bub2-Bfa1 Complex From the Mother-bound Spindle Pole Contributes to Mitotic Exit. J. Cell. Biol. 2006, 172, 335-346.
158. Molk, J. N.; Schuyler, S. C.; Liu, J. Y.; Evans, J. G.; Salmon, E. D.; Pellman, D.; Bloom, K. The Differential Roles of Budding Yeast Tem1p, Cdc15p, and Bub2p Protein Dynamics in Mitotic Exit. Mol. Biol. Cell 2004, 15, 1519-1532.
159. Visintin, R.; Amon, A. Regulation of the Mitotic Exit Protein Kinases Cdc15 and Dbf2. Mol. Biol. Cell 2001, 12, 2961-2974.
160. Visintin, R.; Craig, K.; Hwang, E. S.; Prinz, S.; Tyers, M.; Amon, A. The Phosphatase Cdc14 Triggers Mitotic Exit by Reversal of Cdk-dependent Phosphorylation. Mol. Cell 1998, 2, 709-718.
161. Michel, L.; Liberal, V.; Chatterjee, A.; Kirchweger, R.; Pasche, B.; Gerald, W.; Dobles, M.; Sorger, P. K.; Murty, V. V. V. S.; Benezra, R. MAD2 Haploinsufficiency Causes Premature Anaphase and Chromosome Instability in Mammalian Cells. Nature 2001, 18, 355-359.
162. Warner, S. L.; Gray, P. J.; Von Hoff, D. D. Tubulin-associated Drug Targets: Aurora Kinases, Polo-like Kinases, and Others. Semin. Oncol. 2006, 33, 436-448.
163. Gumireddy, K.; Reddy, M. V.; Cosenza, S. C.; Boominathan, R.; Baker, S. J.; Papathi, N.; Jiang, J.; Holland, J.; Reddy, E. P. ON01910, a Non-ATP-competitive Small Molecule Inhibitor of Plk1, is a Potent Anticancer Agent. Cancer Cell 2005, 7, 275-286.
164. Masuda, Y.; Nishida, A.; Hori, K.; Hirabayashi, T.; Kajimoto, S.; Nakajo, S.; Kondo, T.; Asaka, M.; Nakaya, K. beta-Hydroxyisovalerylshikonin Induces Apoptosis in Human Leukemia Cells by Inhibiting the Activity of a Polo-like Kinase 1 (PLK-1). Oncogene 2003, 22, 1012-1023.
165. Strebhardt, K.; Ullrich, A. Targeting Polo-like Kinase 1 for Cancer Therapy. Nat. Rev. Cancer 2006, 6, 321-330.
166. Liu, Y.; Shreder, K. R.; Gai, W.; Corral, S.; Ferris, D. K.; Rosenblum, J. S. Wortmannin, a Widely Used Phosphoinositide 3-Kinase Inhibitor, Also Potently Inhibits Mammalian Polo-like Kinase. Chem. Biol. 2005, 12, 99-107.
167. Stevenson, C. S.; Capper, E. A.; Roshak, A. K.; Marquez, B.; Eichman, C.; Jackson, J. R.; Mattern, M.; Gerwick, W. H.; Jacobs, R. S.; Marshall, L. A. The Identification and Characterization of the Marine Natural Product Scytonemin as a Novel Antiproliferative Pharmacophore. J. Pharmacol. Exp. Ther. 2002, 303, 858-866.
168. Fischer, P. M.; Lane, D. P. Inhibitors of Cyclin-dependent Kinases as Anticancer Therapeutics. Curr. Med. Chem. 2000, 7, 1213-1245.
169. Harrington, E. A.; Bebbington, D.; Moore, J.; Rasmussen, R. K.; Ajose-Adeogun, A. O.; Nakayama, T.; Graham, J. A.; Demur, C.; Hercend, T.; Diu-Hercend, A.; Su, M.; Golec, J. M. C.; Miller, K. M. VX-680, a Potent and Selective Small-molecule Inhibitor of the Aurora Kinases, Suppresses Tumor Growth In Vivo. Nature Med. 2004, 10, 262-267.
170. Hoar, K.; Chakravarty, A.; Rabino, C.; Wysong, D.; Bowman, D.; Roy, N.; Ecsedy, J. A. MLN-8054, a Small-Molecule Inhibitor of Aurora-A, Causes Spindle Pole and Chromosome Congression Defects Leading to Aneuploidy. Mol. Cell. Biol. 2007, 27, 4513-4525.
171. Fancelli, D.; Berta, D.; Bindi, S.; Cameron, A.; Capella, P.; Carpinelli, P.; Catana, C.; Forte, B.; Giordano, P.; Giorgini, M. L.; Mantegani, S.; Marsiglio, A.; Meroni, M.; Moll, J.; Pittala, V.; Roletto, F.; Severino, D.; Soncini, C.; Storichi, P.; Tonani, R.; Varasi, M.; Vulpetti, A.; Vianello, P. Potent and Selective Aurora Inhibitors Identified by the Expansion of a Novel Scaffold for Protein Kinase Inhibition. J. Med. Chem. 2005, 48, 3080-3084.
172. Soncini, C.; Carpinelli, P.; Gianellini, L.; Fancelli, D.; Vianello, P.; Rusconi, L.; Storici, P.; Zugnoni, P.; Pesenti, E.; Croci, V.; Ceruti, R.; Giorgini, M. L.; Cappella, P.; Ballinari, D.; Sola, F.; Varasi, M.; Bravo, R.; Moll, J. PHA-680632, a Novel Aurora Kinase Inhibitor With Potent Antitumoral Activity. Clin. Cancer Res. 2006, 12, 4080-4089.
173. Schellens, J. H.; Boss, D.; Witteveen, P. O.; Zandvliet, A.; Beijnen, J. H.; Voogel-Fuchs, M.; Morris, C.; Wilson, D.; Voest, E. E. Phase I and Pharmacological Study of the Novel Aurora Kinase Inhibitor AZD1152. J. Clin. Oncol. 2006, 24, 3008.
174. Matthews, N.; Visintin, C.; Hartzoulakis, B.; Jarvis, A.; Selwood, D. L. Aurora A and B Kinases as Targets for Cancer: Will They Be Selective for Tumors? Expert Rev. Anticancer Ther. 2006, 6, 109-120.
175. Dietchfield, C.; Johnson, V. L.; Tighe, A.; Ellston, R.; Haworth, C.; Johnson, T.; Mortlock, A.; Keen, N.; Taylor, S. S. Aurora B Couples Chromosome Alignment With Anaphase by Targeting BubR1, Mad2, and Cenp-E to Kinetochores. J. Cell. Biol. 2003, 161, 267-280.
176. Warner, S. L.; Bashyam, S.; Vankayalapati, H.; Bearss, D. J.; Han, H.; Von Hoff, D. D.; Hurley, L. H. Identification of a Lead Small-molecule Inhibitor of the Aurora Kinases Using a Structure-assisted, Fragment-based Approach. Mol. Cancer Ther. 2006, 5, 1764-1773.
177. Naruganahalli, K. S.; Lakshmanan, M.; Dastidar, S. G.; Ray. A. Therapeutic Potential of Aurora Kinase Inhibitors in Cancer. Curr. Opin. Invest. Drugs 2006, 7, 1044-1051.
178. Jung, F. H.; Pasquet, G.; Lambert-van der Brempt, C.; Lohmann, J. J.; Warin, N.; Renaud, F.; Germain, H.; De Savi, C.; Roberts, N.; Johnson, T.; Dousson, C.; Hill, G. B.; Mortlock, A. A.; Heron, N.; Wilkinson, R. W.; Wedge, S. R.; Heaton, S. P.; Odedra, R.; Keen, N. J.; Green, S.; Brown, E.; Thompson, K.; Brightwell, S. Discovery of Novel and Potent Thiazoloquinazolines as Selective Aurora A and B Kinase Inhibitors. J. Med. Chem. 2006, 49, 955-970.
179. Emanuel, S. L.; Rugg, C. A.; Gruninger, R. H.; Lin, R.; Fuentes-Pesquera, A.; Connolly, P. J.; Wetter, S. K.; Hollister, B.; Kruger, W. W.; Napier, C.; Jolliffe, L.; Middleton, S. A. The In vitro and In vivo Effects of JNJ-7706621: A Dual Inhibitor of Cyclin-Dependent Kinases and Aurora Kinases. Cancer Res. 2005, 65, 9038-9046.
180. Xiao, X. -Y.; Patel, D. V. Kinase Inhibitors. WO Patent: 2006055831. 2006.
181. Mortlock, A.; Jung, F. Substituted Quinazoline Derivatives and their Use as Inhibitors of Aurora-2 kinase. US Patent: 6919338. 2005.
182. Sessa, F.; Mapelli, M.; Ciferri, C.; Tarricone, C.; Areces, L. B.; Schneider, T. R.; Stukenberg, P. T.; Musacchio, A. Mechanism of Aurora B Activation by INCENP and Inhibition by Hesperadin. Mol. Cell. 2005, 18, 379-391.
183. Keen, N.; Taylor, S. Aurora-kinase Inhibitors as Anticancer Agents. Nat. Rev. Cancer 2004, 4, 927-936.
184. Gautschi, O.; Mack, P. C.; Davies, A. M.; Lara, P. N., Jr.; Gandara, D. R. Aurora Kinase Inhibitors: A New Class of Targeted Drugs in Cancer. Clin. Lung Cancer 2006, 8, 93-98.
185. van de Weerdt, B. C.; Medema, R. H. Polo-like kinases: A Team in Control of the Division. Cell Cycle 2006, 5, 853-864.
186. Dai, W.; Cogswell, J. P. Polo-like Kinases and the Microtubule Organization Center: Targets for Cancer Therapies. Prog. Cell Cycle Res. 2003, 5, 327-334.
187. van Vugt, M. A.; Medema, R. H. Getting in and Out of Mitosis With Pololike Kinase-1. Oncogene 2005, 24, 2844-2859.
188. McInnes, C.; Mezna, M.; Fisher, P. M. Progress in the Discovery of Pololike Kinase Inhibitors. Curr. Top. Med. Chem. 2005, 5, 181-197.
189. Katayama, H.; Brinkley, W. R.; Sen, S. The Aurora kinases: Role in Cell Transformation and Tumorigenesis. Cancer Metastasis 2003, 22, 451-464.
190. Paris, J.; Philippe, M. Poly(A) Metabolism and Polysomal Recruitment of Maternal mRNAs During Early Xenopus Development. Dev. Biol. 1990, 140, 221-224.
191. Anand, S.; PenrhynLowe, S.; Venkitaraman, A. R. Aurora-A Amplification Overrides the Mitotic Spindle Assembly Checkpoint, Inducing Resistance to Taxol. Cancer Cell 2003, 3, 51-62.
192. Cheetham, G. M.; Knegtel, R. M.; Coll, J. T.; Renwick, S. B.; Swenson, L.; Weber, P.; Lippke, J. A.; Austen, D. A. Crystal Structure of Aurora-2, an Oncogenic Serine/threonine Kinase. J. Biol. Chem. 2002, 277, 42419-42422.
193. Meraldi, P.; Honday, R.; Niggy, E. A. Aurora Kinases Link Chromosome Segregation and Cell Division to Cancer Susceptibility. Curr. Opin. Gen. Dev. 2004, 14, 29-36.
194. Sugimoto, K.; Urano, T.; Zushi, H.; Inoue, K.; Tasaka, H.; Tachibana, M.; Dotsu, M. Molecular Dynamics of Aurora-A Kinase in Living Mitotic Cells Simultaneously Visualized With Histone H3 and Nuclear Membrane Protein Importin. Cell Struct. Funct. 2002, 27, 457-467.
195. Carmena, M.; Earnshaw, W. C. The Cellular Geography of Aurora Kinases. Nature Rev. Mol. Cell Biol. 2003, 4, 842-854.
196. Bischoff, J. R.; Anderson, L.; Zhu, Y.; Mossie, K.; Ng, L.; Souzza, B.; Schryver, B.; Flanagan, P.; Clairvoyant, F.; Ginther, C.; Chan, C. S. M.; Novotny, M.; Slamon, D. J.; Plowman, G. D. A Homologue of Drosophila Aurora Kinase is Oncogenic and Amplified in Human Colorectal Cancers. EMBO J. 1998, 17, 3052-3065.
197. Courjal, F.; Cuny, M.; Rodriguez, C.; Louason, G.; Speiser, P.; Katsaros, D.; Tanner, M. M.; Zeillinger, R.; Theillet, C. DNA Amplifications at 20q13 and MDM2 Define Distinct Subsets of Evolved Breast and Ovarian Tumours. Br. J. Cancer 1996, 74, 1984-1989.
198. Royce, M. E.; Xia, W.; Sahin, A. A.; Katayama, H.; Johnston, D. A.; Hortobagyi, G.; Sen, S.; Hung, M. C. STK15/Aurora-A Expression in Primary Breast Tumors is Correlated With Nuclear Grade but not With Prognosis. Cancer 2004, 100, 12-19.
199. Anand, S.; PenrhynLowe, S.; Venkitaraman, A. R. Aurora-A Amplification Overrides the Mitotic Spindle Assembly Checkpoint, Inducing Resistance to Taxol. Cancer Cell 2003, 3, 51-62.
200. Kallio, M. J.; McCleland, M. L.; Stukenberg, P. T.; Gorbsky, G. J. Inhibition of Aurora B Kinase Blocks Chromosome Segregation, Overrides the Spindle Checkpoint, and Perturbs Microtubule Dynamics in Mitosis. Curr. Biol. 2002, 12, 900-905.
201. Li, F. Survivin Study: What is the Next Wave? J. Cell. Physiol. 2003, 197, 8-29.
202. Mortlock, A.; Keen, N. J.; Jung, F. H.; Heron, N. M.; Foote, K. M.; Wilkinson, R.; Green, S. Progress in the Development of Selective Inhibitors of Aurora Kinases. Curr. Top. Med. Chem. 2005, 5, 199-213.
203. Ditchfield, C.; Johnson, V. L.; Tighe, A.; Ellston, R.; Haworth, C.; Johnson, T.; Mortlock, A.; Keen, N.; Taylor S. S. Aurora B Couples Chromosome Alignment With Anaphase by Targeting BubR1, Mad2, and Cenp-E to Kinetochores. J. Cell. Biol. 2003, 161, 267-280.
204. Hauf, S.; Cole, R. W.; LaTerra, S.; Zimmer, C.; Schnapp, G.; Walter, R.; Heckel, A.; van Meel, J.; Rieder, C. L.; Peters, J. -M. The Small Molecule Hesperadin Reveals a Role for Aurora B in Correcting Kinetochoremicrotubule Attachment and in Maintaining the Spindle Assembly Checkpoint. J. Cell. Biol. 2003, 161, 281-294.
205. Kiselyov, A.; Balakin, K.V.; Tkachenko, S. E.; Savchuk, N.; Ivachtchenko, A. V. Recent Progress in Discovery and Development of Antimitotic agents. Anticancer Agents Med. Chem. 2007, 7, 189-208.
206. Dashyant, D.; Newlander, K. A. Azaindole Inhibitors of Aurora Kinases. US Patent 20070149561, 2007;
207. see also: Bhide, R. S. ; Ruel, R. T.; Thibault, C.; L'Heureux, A. Azaindole Kinase Inhibitors. US Patent 6969717, 2005.
208. Peters, J. M. The Anaphase Promoting Complex/cyclosome: A Machine Designed to Destroy. Nat. Rev. Mol. Cell Biol. 2006, 7, 644-56.
209. Wirth, K. G.; Wutz, G.; Kudo, N. R.; Desdouets, C.; Zetterberg, A.; Taghybeeglu, S.; Seznec, J.; Ducos, G. M.; Ricci, R.; Firnberg, N.; Peters, J. M.; Nasmyth, K. Separase: A Universal Trigger for Sister Chromatid Disjunction but not Chromosome Cycle Progression. J. Cell Biol. 2006, 172, 847-860.
210. Agarwal, R.; Cohen-Fix, O. Mitotic Regulation: The Fine Tuning of Separase Activity. Cell Cycle 2002, 1, 255-257.
211. Huang, X.; Hatcher, R.; York, J. P.; Zhang, P. Securin and Separase Phosphorylation Act Redundantly to Maintain Sister Chromatid Cohesion in Mammalian Cells. Mol. Biol. Cell 2005, 16, 4725-4732.
212. Attard, G.; Greystoke, A.; Kaye, S.; De Bono, Update on Tubulin-binding Agents. J. Pathol. Biol. 2006, 54, 72-84.
213. Rieder, C. L.; Maiato, H. Stuck in Division or Passing Through: What Happens When Cells Cannot Satisfy the Spindle Assembly Checkpoint. Dev. Cell 2004, 7, 637-651.
214. Gurzov, E. N.; Izquierdo, M. RNA Interference Against Hec1 Inhibits Tumor Growth In Vivo. Gene Ther. 2006, 13, 1-7.
215. Marko, J.; Kallio, V. A.; Beardmore, J. W.; Gary, J. G. Rapid Microtubule-independent Dynamics of Cdc20 at Kinetochores and Centrosomes in Mammalian Cells. J. Cell Biol. 2002, 158, 841-847.
216. Andersen, M. H.; Soerensen, R. B.; Becker, J. C.; Per, T. S. HLA-A24 and Survivin: Possibilities in Therapeutic Vaccination Against Cancer. J. Transl. Med. 2006, 4, 38-44.
217. Scolnick, D. M.; Halazonetis, T. D. Chfr Defines a Mitotic Stress Checkpoint that Delays Entry Into Metaphase. Nature 2000, 406, 430-437.
218. Fisk, H. A.; Mattison, C. P.; Winey, M. Human Mps1 Protein Kinase is Required for Centrosome Duplication and Normal Mitotic Progression. Proc. Natl. Acad. Sci. USA 2003, 100, 14875-14880.
219. Hayward, D. G.; Fry, A. M. Nek2 Kinase in Chromosome Instability and Cancer. Cancer Lett. 2006, 237, 155-166.
220. Shiina, N.; Tsukita, S. Regulation of Microtubule Organization During Interphase and M phase. Cell Struct. Funct. 1999, 24, 385-391.
221. Lenart, P.; Peters, J. M. Checkpoint Activation: Don't Get Mad Too Much. Curr. Biol. 2006, 16, R412-R414.
222. Piatti, S.; Venturetti, M.; Chiroli, E.; Fraschini, R. The Spindle Position Checkpoint in Budding Yeast: The Motherly Care of MEN. Cell Div. 2006, 1, 2.
223. Guertin, D. A.; Chang, L.; Irshad, F.; Gould, K. L.; McCollum, D. The Role of the Sid1p Kinase and Cdc14p in Regulating the Onset of Cytokinesis in Fission Yeast. EMBO J. 2000, 19, 1803-1815.
224. Kramer, E. R.; Scheuringer, N.; Podtelejnikov, A. V.; Mann, M.; Peters, J. M. Mitotic Regulation of the APC Activator Proteins CDC20 and CDH1. Mol. Biol. Cell 2000, 11, 1555-1569.