Update on Aurora kinase inhibitors in gynecologic malignancies

Recent Patents on Anti-Cancer Drug Discovery

Volumn 3, Issue 3, 2008, Pages 162-177

  Tao, Xia ^a,b   Chon, Hye S ^c   Fu, Siqing ^a   Kavanagh, John J ^a   Hu, Wei ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b PEKING UNIVERSITY FIRST HOSPITAL   (China)

^c BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

Aurora kinase inhibitors; Aurora kinases; Gynecologic malignancies

Indexed keywords

4 [[9 CHLORO 7 (2,6 DIFLUOROPHENYL) 5H PYRIMIDO[5,4 D][2]BENZAZEPIN 2 YL]AMINO]BENZOIC ACID; 7 ETHYL 10 HYDROXYCAMPTOTHECIN; AT 9283; AURORA A KINASE; AURORA B KINASE; AURORA KINASE INHIBITOR; BCR ABL PROTEIN; CCT 129202; CYC 116; CYCLOPROPANECARBOXYLIC ACID [4 [4 (4 METHYL 1 PIPERAZINYL) 6 (5 METHYL 2H PYRAZOL 3 YLAMINO) 2 PYRIMIDINYLTHIO]PHENYL]AMIDE; DAUNORUBICIN; DEXAMETHASONE; DOCETAXEL; ENMD 2076; FLUOROURACIL; GEMCITABINE; HESPERADIN; IRINOTECAN; N [4 [6 METHOXY 7 (3 MORPHOLINOPROPOXY) 4 QUINAZOLINYLAMINO]PHENYL]BENZAMIDE; N [5 (2 METHOXY 2 PHENYLACETYL) 1,4,5,6 TETRAHYDROPYRROLO[3,4 C]PYRAZOL 3 YL] 4 (4 METHYLPIPERAZIN 1 YL)BENZAMIDE; NAVELBINE; OXALIPLATIN; PHA 680632; PHA 739358; PROTEIN KINASE INHIBITOR; PYRIMIDINONE DERIVATIVE; R 763; RESVERATROL; UNCLASSIFIED DRUG; UNINDEXED DRUG; VE 465; VINCRISTINE;

ANTINEOPLASTIC ACTIVITY; CANCER INHIBITION; CARCINOGENESIS; CHROMOSOME SEGREGATION; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; CONTINUOUS INFUSION; CYTOKINESIS; DRUG DOSE ESCALATION; DRUG POTENTIATION; DRUG TARGETING; DRUG WITHDRAWAL; FEMALE GENITAL TRACT TUMOR; GENE OVEREXPRESSION; HUMAN; LYMPHOCYTOPENIA; NEUTROPENIA; NONHUMAN; PATENT; PNEUMONIA; PRIORITY JOURNAL; PROGNOSIS; REGULATORY MECHANISM; REVIEW; SEPTICEMIA; SINGLE DRUG DOSE; SOMNOLENCE; THROMBOCYTOPENIA;

ANIMALS; ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; DRUG DELIVERY SYSTEMS; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GENITAL NEOPLASMS, FEMALE; HUMANS; PATENTS AS TOPIC; PROTEIN-SERINE-THREONINE KINASES;

EID: 58049219029     PISSN: 15748928     EISSN: None     Source Type: Journal    
DOI: 10.2174/157489208786242322     Document Type: Review

References (185)

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin 2008; 58: 71-96.
2. Harries M, Kaye SB. Recent advances in the treatment of epithelial ovarian cancer. Expert Opin Investig Drugs 2001; 10: 1715-1724.
3. Elit L, Hirte H. Current status and future innovations of hormonal agents, chemotherapy and investigational agents in endometrial cancer. Curr Opin Obstet Gynecol 2002; 14: 67-73.
4. Waggoner SE. Cervical cancer. Lancet 2003; 361: 2217-2225.
5. Hamada K, Shirakawa T, Gotoh A, et al. Adenovirus-mediated transfer of human papillomavirus 16 E6/E7 antisense RNA and induction of apoptosis in cervical cancer. Gynecol Oncol 2006; 103: 820-830.
6. Glover DM, Leibowitz MH, McLean DA, et al. Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell 1995; 81: 95-105.
7. Bischoff JR, Anderson L, Zhu Y, et al. A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J 1998; 17: 3052-3065.
8. Kimura M, Matsuda Y, Yoshioka T, et al. Cell cycle-dependent expression and centrosome localization of a third human aurora/ Ip11-related protein kinase, AIK3. J Biol Chem 1999; 274: 7334-7340.
9. Terada Y, Tatsuka M, Suzuki F, et al. AIM-1: a mammalian midbody-associated protein required for cytokinesis. EMBO J 1998; 17: 667-676.
10. Ducat D, Zheng Y. Aurora kinases in spindle assembly and chromosome segregation. Exp Cell Res 2004; 301: 60-67.
11. Fu J, Bian M, Jiang Q, et al. Roles of Aurora kinases in mitosis and tumorigenesis. Mol Cancer Res 2007; 5: 1-10.
12. Hirota T, Kunitoku N, Sasayama T, et al. Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells. Cell 2003; 114: 585-598.
13. Giet R, McLean D, Descamps S, et al. Drosophila Aurora A kinase is required to localize D-TACC to centrosomes and to regulate astral microtubules. J Cell Biol 2002; 156: 437-451.
14. Barros TP, Kinoshita K, Hyman AA, et al. Aurora A activates D-TACC-Msps complexes exclusively at centrosomes to stabilize centrosomal microtubules. J Cell Biol 2005; 170: 1039-1046.
15. Lee MJ, Gergely F, Jeffers K, et al. Msps/XMAP215 interacts with the centrosomal protein D-TACC to regulate microtubule behaviour. Nat Cell Biol 2001; 3: 643-649.
16. Kufer TA, Sillje HH, Korner R, et al. Human TPX2 is required for targeting Aurora-A kinase to the spindle. J Cell Biol 2002; 158: 617-623.
17. Tsai MY, Wiese C, Cao K, et al. A Ran signalling pathway mediated by the mitotic kinase Aurora A in spindle assembly. Nat Cell Biol 2003; 5: 242-248.
18. Marumoto T, Honda S, Hara T, et al. Aurora-A kinase maintains the fidelity of early and late mitotic events in HeLa cells. J Biol Chem 2003; 278: 51786-51795.
19. Andrews PD, Ovechkina Y, Morrice N, et al. Aurora B regulates MCAK at the mitotic centromere. Dev Cell 2004; 6: 253-268.
20. Lan W, Zhang X, Kline-Smith SL, et al. Aurora B phosphorylates centromeric MCAK and regulates its localization and microtubule depolymerization activity. Curr Biol 2004; 14: 273-286.
21. Vigneron S, Prieto S, Bernis C, et al. Kinetochore localization of spindle checkpoint proteins: who controls whom? Mol Biol Cell 2004; 15: 4584-4596.
22. Li X, Sakashita G, Matsuzaki H, et al. Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C. J Biol Chem 2004; 279: 47201-47211.
23. Sasai K, Katayama H, Stenoien DL, et al. Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells. Cell Motil Cytoskeleton 2004; 59: 249-263.
24. Yan X, Cao L, Li Q, et al. Aurora C is directly associated with Survivin and required for cytokinesis. Genes Cells 2005; 10: 617-626.
25. Meraldi P, Honda R, Nigg EA. Aurora kinases link chromosome segregation and cell division to cancer susceptibility. Curr Opin Genet Dev 2004; 14: 29-36.
26. Katayama H, Brinkley WR, Sen S. The Aurora kinases: Role in cell transformation and tumorigenesis. Cancer Metastasis Rev 2003; 22: 451-464.
27. Du J, Hannon GJ. The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1. Nucleic Acids Res 2002; 30: 5465-5475.
28. Meraldi P, Honda R, Nigg EA. Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells. EMBO J 2002; 21: 483-492.
29. Katayama H, Sasai K, Kawai H, et al. Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet 2004; 36: 55-62.
30. Yang H, Ou CC, Feldman RI, et al. Aurora-A kinase regulates telomerase activity through c-Myc in human ovarian and breast epithelial cells. Cancer Res 2004; 64: 463-467.
31. Tatsuka M, Sato S, Kitajima S, et al. Overexpression of Aurora-A potentiates HRAS-mediated oncogenic transformation and is implicated in oral carcinogenesis. Oncogene 2005; 24: 1122-1127.
32. Yu X, Minter-Dykhouse K, Malureanu L, et al. Chfr is required for tumor suppression and Aurora A regulation. Nat Genet 2005; 37: 401-406.
33. Tanner MM, Grenman S, Koul A, et al. Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer. Clin Cancer Res 2000; 6: 1833-1839.
34. Gritsko TM, Coppola D, Paciga JE, et al. Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer. Clin Cancer Res 2003; 9: 1420-1426.
35. Hu W, Kavanagh JJ, Deaver M, et al. Frequent overexpression of STK15/Aurora-A/BTAK and chromosomal instability in tumorigenic cell cultures derived from human ovarian cancer. Oncol Res 2005; 15: 49-57.
36. Landen CN, Lin YG, Immaneni A, et al. Overexpression of the centrosomal protein Aurora-A kinase is associated with poor prognosis in epithelial ovarian cancer patients. Clin Cancer Res 2007; 13: 4098-4104.
37. Kulkarni AA, Loddo M, Leo E, et al. DNA replication licensing factors and aurora kinases are linked to aneuploidy and clinical outcome in epithelial ovarian carcinoma. Clin Cancer Res 2007; 13: 6153-6161.
38. Lassmann S, Shen Y, Jutting U, et al. Predictive value of Aurora-A/STK15 expression for late stage epithelial ovarian cancer patients treated by adjuvant chemotherapy. Clin Cancer Res 2007; 13: 4083-4091.
39. Yang H, He L, Kruk P, et al. Aurora-A induces cell survival and chemoresistance by activation of Akt through a p53-dependent manner in ovarian cancer cells. Int J Cancer 2006; 119: 2304-2312.
40. Linardopoulos S. Aurora-A kinase regulates NF-kappaB activity: lessons from combination studies. J BUON 2007; 12 Suppl 1: S67-70.
41. Miyashita T, Krajewski S, Krajewska M, et al. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene 1994; 9: 1799-1805.
42. Zhang Z, Singh M, Davidson S, et al. Activation of BTAK expression in primary ovarian surface epithelial cells of prophylactic ovaries. Mod Pathol 2007; 20: 1078-1084.
43. Moreno-Bueno G, Sanchez-Estevez C, Cassia R, et al. Differential gene expression profile in endometrioid and nonendometrioid endometrial carcinoma: STK15 is frequently overexpressed and amplified in nonendometrioid carcinomas. Cancer Res 2003; 63: 5697-5702.
44. Kurai M, Shiozawa T, Shih HC, et al. Expression of Aurora kinases A and B in normal, hyperplastic, and malignant human endometrium: Aurora B as a predictor for poor prognosis in endometrial carcinoma. Hum Pathol 2005; 36: 1281-1288.
45. Zhou H, Kuang J, Zhong L, et al. Tumour amplified kinase STK15/ BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet 1998; 20: 189-193.
46. Fu S, Hu W, Kavanagh JJ, et al. Targeting Aurora kinases in ovarian cancer. Expert Opin Ther Targets 2006; 10: 77-85.
47. Carvajal RD, Tse A, Schwartz GK. Aurora kinases: new targets for cancer therapy. Clin Cancer Res 2006; 12: 6869-6875.
48. Hata T, Furukawa T, Sunamura M, et al. RNA interference targeting aurora kinase a suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells: Cancer Res 2005, 65: 2899-2905.
49. http://www.entremed.com/files/aacr-2008finaloutactual.pdf.
50. Ravandi F, Foran J, Verstovsek S, et al. A phase I trial of AT9283, a multitargeted kinase inhibitor, in patients with refractory hematological malignancies. Blood 2007;110
51. http://www.astex-therapeutics.com/event_pdfs/ ASH%20Astex%20AT9283%20Clinical%20final%20A3.pdf.
52. Evans RP, Naber C, Steffler T, et al. The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma. Br J Haematol 2008; 140: 295-302.
53. Tao Y, Zhang P, Girdler F, et al. Enhancement of radiation response in p53-deficient cancer cells by the Aurora-B kinase inhibitor AZD1152. Oncogene 2008; 27(23): 3244-55.
54. Wilkinson RW, Odedra R, Heaton SP, et al. AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis. Clin Cancer Res 2007; 13: 3682-3688.
55. Yang J, Ikezoe T, Nishioka C, et al. AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo. Blood 2007; 110: 2034-2040.
56. Mortlock AA, Foote KM, Heron NM, et al. Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase. J Med Chem 2007; 50: 2213-2224.
57. Tao Y, Frascogna V, Zhang P, et al. Enhancement of radiation response in p53-deficient cancer cells in vivo using different schedules of the Aurora B kinase inhibitor AZD1152 and irradiation. AACR Annual meeting 2008
58. Nair JS TA, Keen N, Schwartz GK. A novel aurora b kinase inhibitor with potent anticancer activity either as a single agent or in combination with chemotherapy. J Clin Oncol 2004; 22 (14S)
59. Schellens JH, Boss D, Witteveen PO, et al. Phase I and pharmacological study of the novel aurora kinase inhibitor AZD1152. J Clin Oncol 2006; 24(18S)
60. LeRoy PJ, Hunter JJ, Hoar KM, et al. Localization of human TACC3 to mitotic spindles is mediated by phosphorylation on Ser558 by Aurora A: a novel pharmacodynamic method for measuring Aurora A activity. Cancer Res 2007; 67: 5362-5370.
61. Hoar K, Chakravarty A, Rabino C, et al. MLN8054, a small-molecule inhibitor of Aurora A, causes spindle pole and chromosome congression defects leading to aneuploidy. Mol Cell Biol 2007; 27: 4513-4525.
62. Manfredi MG, Ecsedy JA, Meetze KA, et al. Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase. Proc Natl Acad Sci USA 2007; 104: 4106-4111.
63. Chng WJ, Braggio E, Mulligan G, et al. The centrosome index is a powerful prognostic marker in myeloma and identifies a cohort of patients that might benefit from aurora kinase inhibition. Blood 2008; 111: 1603-1609.
64. Mountzios G, Terpos E, Dimopoulos MA. Aurora kinases as targets for cancer therapy. Cancer Treat Rev 2008; 34: 175-182.
65. Jones SF, Cohen RB, Dees EC, et al. Phase I clinical trial of MLN8054, a selective inhibitor of Aurora A kinase. J Clin Oncol 2007; 25(18S)
66. Gontarewicz A, Balabanov S, Keller G, et al. Simultaneous targeting of Aurora kinases and Bcr-Abl kinase by the small molecule inhibitor PHA-739358 is effective against imatinib-resistant BCR-ABL mutations including T3151. Blood 2008; 111: 4355-4364.
67. Carpinelli P, Ceruti R, Giorgini ML, et al. PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer. Mol Cancer Ther 2007; 6: 3158-3168.
68. Modugno M, Casale E, Soncini C, et al. Crystal structure of the T3151 Abl mutant in complex with the aurora kinases inhibitor PHA-739358. Cancer Res 2007; 67: 7987-7990.
69. http://www.clinicaltrials.gov/ct2/results?term=pha739358.
70. Paquette RL, Shah NP, Sawyers CL, et al. Pha-739358, an aurora kinase inhibitor, induces clinical responses in chronic myeloid leukemia harboring t315i mutations of bcr-abl. Blood 2007; 110
71. http://www.clinicaltrials.gov/ct2/results?term=r763.
72. http://www.rigel.com/rigel/oncology.
73. Gizatullin F, Yao-Y, Kung V, et al. The Aurora kinase inhibitor VX-680 induces endoreduplication and apoptosis preferentially in cells with compromised p53-dependent postmitotic checkpoint function. Cancer-Res 2006; 66: 7668-7677.
74. Young MA, Shah NP, Chao LH, et al. Structure of the kinase domain of an imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680. Cancer Res 2006; 66; 1007-1014.
75. Harrington EA, Bebbington D, Moore J, et al. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med 2004; 10: 262-267.
76. Lavelle F. The Aurora kinase inhibitor VX680, leader, of a new family of antitumoral agents. Bull Cancer 2004; 91: 300-301.
77. Lee EC, Frolov A, Li R, et al. Targeting Aurora kinases for the treatment of prostate cancer. Cancer Res 2006; 66: 4996-5002.
78. Guan Z, Wang XR, Zhu XF, et al. Aurora-A, a negative prognostic marker, increases migration and decreases radiosensitivity in cancer cells. Cancer Res 2007; 67: 10436-10444.
79. Tyler RK, Shpiro N, Marquez R, et al. VX-680 inhibits Aurora A and Aurora B kinase activity in human cells. Cell Cycle 2007; 6: 2846-2854.
80. Huang XF, Luo SK, Xu J, et al. Aurora kinase inhibitory VX-680 increases Bax/Bcl-2 ratio and induces apoptosis in Aurora-A-high acute myeloid leukemia. Blood 2008; 111: 2854-2865.
81. Cheetham GM, Charlton PA, Golec JM, et al. Structural basis for potent inhibition of the Aurora kinases and a T3151 multi-drug resistant mutant form of Abl kinase by VX-680. Cancer Lett 2007; 251: 323-329.
82. Hoover RR, Harding MW. Activity of the aurora kinase inhibitor MK-0457 (VX-680) in combination with taxotere. J Clin Oncol 2007; 25 (18S)
83. Lin YG, Merritt WM, Fiterman DJ, et al. Targeting aurora kinase inhibits tumorigenesis in ovarian cancer. Gynel Oncol 2007; 107: 360-361.
84. Giles FJ, Cortes J, Jones D, et al. MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T3151 BCR-ABL mutation. Blood 2007; 109: 500-502.
85. Rubin EH, Shapiro GI, Stein MN, et al. A phase I clinical and pharmacokinetic (PK) trial of the aurora kinase (AK) inhibitor MK-0457 in cancer patients. J Clin Oncol 2006; 24 (18S)
86. http://www.pharmaprojects.com/news/2911_1647.htm.
87. http://www.marketwatch.com/news/story/ vertex-pharmaceuticals-reviews-clinical-advancements/ story.aspx?guid=%7BCD94A83B-D315-46B8-904F-4CBEAE0014DB%7D&dist= TQP_Mod_preessN.
88. http://www.clinicaltrials.gov/ct2/results?term=cyc116.
89. http://clinicaltrials.gov/ct2/results?term=MLN8237.
90. http://www.clinicaltrials.gov/ct2/results?term=PF-03814735+.
91. Evanchik MJ, Hogan JN, Arbitrario JP, et al. SNS-314, a potent inhibitor of aurora kinases, has preclinical anti-tumor activity and induces apoptosis. AACR Annual meeting, 2008
92. http://clinicaltrials.gov/ct2/results?term=SNS-314.
93. http://www.clinicaltrials.gov/ct2/results?term=aurora+kinase+inhibitor.
94. http://www.astex-therapeutics.com/event_pdfs/ ASH%20Astex%20AT9283%20Clinical%20final%20A3.pdf.
95. http://www.clinicaltrials.gov/ct2/results?term=AT9283.
96. http://www.clinicaltrials.gov/ct2/results?term-azd1152.
97. http://clinicaltrials.gov/ct2/results?term=MLN8054.
98. http://www.clinicaltrials.gov/ct2/results?term=VX-680+.
99. Chan F, Sun C, Perumal M, et al. Mechanism of action of the Aurora kinase inhibitor CCT129202 and in vivo quantification of biological activity. Mol Cancer Ther 2007; 6: 3147-3157.
100. MacCallum DE, Melville J, Watt K, et al. Combination studies with the oral Aurora kinase inhibitor CYC116 and chemotherapeutic agents. AACR Annual meeting 2008
101. Griffiths G, Tosh C, Kollareddy M, et al. The basis of cell sensitivity to Aurora A/B Inhibitors. AACR Annual meeting 2008;
102. Griffiths G, Scaerou F, Sorrell D, et al. Anti-tumor activity of CYC116, a novel small molecule inhibitor of Aurora kinases and VEGFR2. AACR Annual meeting 2008
103. http://news.moneycentral.msn.com/ticker/article.aspx?Feed=BW&Date= 20080416&ID=8495766&Symbol=CYCC.
104. http://www.abstractsonline.com/viewer/SearchResults.asp.
105. http://www.entremed.com/news/entremeds-kinase-inhibitor-enmd- 2076-presented-during-aacr-special-session.
106. Hauf S, Cole RW, LaTerra 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: 281-294.
107. Miyauchi K, Zhu X, Foong C, et al. Aurora B kinase activity is required to prevent polar cortical ingression during cytokinesis. Cell Cycle 2007; 6: 2549-2553.
108. Sakita-Suto S, Kanda A, Suzuki F, et al. Aurora-B regulates RNA methyltransferase NSUN2. Mol Biol Cell 2007; 18: 1107-1117.
109. Tao Y, Zhang P, Frascogna V, et al. Enhancement of radiation response by inhibition of Aurora-A kinase using siRNA or a selective Aurora kinase inhibitor PHA680632 in p53-deficient cancer cells. Br J Cancer 2007; 97: 1664-1672.
110. Soncini C, Carpinelli P, Gianellini L, et al. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Res 2006; 12: 4080-4089.
111. Fancelli D, Berta D, Bindi S, et al. Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem 2005; 48: 3080-3084.
112. Evans R, Naber C, Steffler T, et al. Aurora A kinase RNAi and small molecule inhibition of Aurora kinases with VE-465 induce apoptotic death in multiple myeloma cells. Leuk Lymphoma 2008; 49: 559-569.
113. Negri JM, McMilin DW, Mitsiades N. Anti-myeloma activity of the small-molecule aurora kinase inhibitor VE465. Blood 2006; 108
114. Ditchfield C, Johnson VL, Tighe A, et al. Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell Biol 2003; 161: 267-280.
115. Ikezoe T, Yang J, Nishioka C, et al. A novel treatment strategy targeting Aurora kinases in acute myelogenous leukemia. Mol Cancer Ther 2007; 6: 1851-1857.
116. Gadea BB, Ruderman JV. 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: 1305-1318.
117. Keen N, Taylor S. Aurora-kinase inhibitors as anticancer agents. Nat Rev Cancer 2004; 4: 927-936.
118. Emanuel S, Rugg CA, Gruninger RH, et al. 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.
119. Seamon JA, Rugg CA, Emanuel S, et al. Role of the ABCG2 drug transporter in the resistance and oral bioavailability of a potent cyclin-dependent kinase/Aurora kinase inhibitor. Mol Cancer Ther 2006; 5: 2459-2467.
120. http://www.entremed.com/?s=MKC-1693.
121. http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=109&STORY=/www/ story/05-13-2005/0003600071&EDATE=.
122. Warner SL, Bashyam S, Vankayalapati H, et al. 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.
123. Clifford AB, Grand CL, Vankayalapati H, et al. Discovery and development of MP529, a new effective and selective inhibitor of Aurora A kinase. AACR, 2008: poster 3261.
124. Vankayalapati H, Grand CL, Liu XH, et al. A potent small molecule PIM kinase inhibitor with activity in cell lines from hematological and solid malignancies. AACR Annual Meeting, 2008: poster 5729.
125. Breur JG, Reagan-Shaw SR, Ahmad N. Prostate cancer chemopreventive effects of resveratrol are mediated via down-modulation of mitosis kinases Polo-like kinase 1, Aurora-A and Aurora-B. Proc Amer Assoc Cancer Res 2005; 46
126. http://www.crimsoncanary.com/Documents/Aurora_Kinase.pdf.
127. Claiborne, C.F., Sells, T.B., Stroud, S.G.: WO08021038 (2008).
128. Clark, M.: WO08016547 (2008).
129. MacCallum, D., Green, S.: WO07132221 (2007).
130. Lewis, J.: WO07115805 (2007).
131. Lewis, J., Conti, E., Jeyappakash, A.A.: WO07113005 (2007).
132. Fancelli, D., Moll, J., Pulici, M., Quartieri, F., Bandiera, T.: WO07009898 (2007).
133. Chiu, G., Li, S.J., Connally, P.J., Middleton, S.A., Emanuel, S.L., Huang, S.L., Lin, R.H., Lu, Y.H.: WO06130673 (2006).
134. Okram, B., Ren, P., Gray, N.S.: WO06124863 (2006).
135. Davidson, A.H., Drummond, A.H., Davies, S.: WO06117570 (2006).
136. Davidson, A.H., Davies, S.J., Moffat, D.F.C.: WO06117552 (2006).
137. Fischer, P.M., Wang, S.D., Meades, C.K., Andrews, M.J.I., Gibson, D., Duncan, K.: WO06075152 (2006).
138. Berdini, V., O'brien, M.A., Carr, M.G., Davies, N.G.M., Gill, A.L., Navarro, E.F., Howard, S., Trewartha, G., Woodhead, A.J., Woolford, A.J.A., Wyatt, P.G.: WO06070198 (2006).
139. Berdini, V., Carr, M.G., Gill A.L., Howard, S., Navarro, E.F., Trewartha, G., Rees, D.C., Vinkovic, M., Wyatt, P.G.: WO06070195 ( 2006).
140. Berdini, V., O'brien, M.A., Phillips, T.R., Wyatt, P.G.: WO06070192 ( 2006).
141. Foote, K.M.: WO06067391 (2006).
142. Binch, H., Robinson, D., Miller, A., Fraysse, D.: WO06058074 (2006).
143. Xiao, X.Y., Patel, D.V.: WO06055831 (2006).
144. Argade, A., Singh, R., Li, H.: WO0606055561 (2006).
145. Wan, Y.Q., Mi, Y., Fan, Y., Cheng, D., Liu, Y., Gray, N.S., Albaugh, P.A.: WO06052936 (2006).
146. Huang, S.L., Lin, R.H., Connolly, P.J., Emanuel, S.L., Middleton, S.A.: WO06050076 (2006).
147. Ohkubo, M., Kato, T., Kawanishi, N., Mita, T., Shimomura, T.: WO06046735 (2006).
148. Dong, Q., Hosfield, D., Paraselli, B.R., Scorah, N., Stafford, J.A., Wallace, M., Zhang, Z.Y.: WO06044687 (2006).
149. Blackburn, C., Claiborne, C.F., Cullis, C.A., Dales, N.A., Patane, M.A., Stirling, M., Stradella, O.G., Weatherhead, G.S.: WO06041773 (2006).
150. Liu, J., Patch, R.J., Player, M.R.: WO06036883 (2006).
151. Lew, W., Baskaran, S., Oslob, J.D., Yoburn, J., Zhong, M.: WO06036266 (2006).
152. Boyd, E., Brookfield, F., Georges, G., Goller, B., Huensch, S., Rueger, P., Rueth, M., Scheiblich, S., Schuell, C., Von Der, S.W., Warne, J., Weigand, S.: WO06032518 (2006).
153. Arnold, W.D., Gosberg, A., Li, Z., Steensma, R.W., Wilson, M.E.: WO06015124 (2006).
154. Arnold, W.D., Bounaud, P., Gosberg, A., Li, Z., McDonald, I., Steensma, R.W., Wilson, M.E.: WO06015123 (2006).
155. Gill, A.L., Carr, M.G., O'brien, M.A., Wyatt, P.G., Berdini, V.: WO066003440 (2006).
156. Halley, F., Tabart, M., Bouchard, H., Souaille, C., Le Brun, A., Viviani, F., Gauzy-Lazo, L., Desmazeau, P., Angouillant-Boniface, O., Filoche-Romme, B.: WO6003276 (2006).
157. Sependa, G.J., Storey, R.: US20080045481 (2008).
158. Binch, H., Mortimore, M., Fraysse, D., Rutherford, A.: US2008032963 ( 2008).
159. Ehlert, J., Herz, T., Krauss, R., Kubbutat, M., Lang, M., Saeb, W., Schaechtele, C., Tasler, S., Totzke, F., Zirrgiebel, U.: US0021446 ( 2007).
160. Wang, S.D., Mclachlan, J., Gibson, D., Causton, A., Turner, N.J., Fischer, P.M.: US0021419 (2007).
161. Heron, N.M., Pasquet, G.R., Mortlock, A.A., Jung, F.H.: US20060270692 (2006).
162. McInnes, C., Thomas, M.P., Wang, S.D., McIntyre, N., Westwood, N., Fischer, P.M.: US20060264628 (2006).
163. Bebbington, D., Knegtel, R., Binch, H., Golec, J.M.C., Li, P., Charrier, J.D.: US20060258658 (2006).
164. Wang, S.D., Meades, C.K., Gibson, D., Fischer, P.M.: US20060241297 ( 2006).
165. Binch, H., Fraysse, D., Robinson, D.: US2006166936 (2006).
166. Tonani, R., Bindi, S., Fancelli, D., Pittala', V., D', A.M.: US20060160874 (2006).
167. Herz, T., Krauss, R., Kubbutat, M., Lang, M., Schaechtele, C, Tasler, S., Totzke, F.: US20060142570 (2006).
168. Plowman, G.D., Whyte, D., Manning, G., Sudarsanam, S., Martinez, R.: US20060140954 (2006).
169. Mortlock, A.A., Heron, N.M., Jung, F.H., Pasquet, G.R: US20060135541 ( 2006).
170. Knegtel, R., Jimenez, J.M., Charrier, J.D., Stamos, D., Li, P., Come, J., Aronov. A.: US20060135537 (2006).
171. Liu, J., Patch, R.J., Player, M.R.: US20060106022 (2006).
172. Paruch, K., Guzi, T.J., Dwyer, M.P., Shipps, Jr. G.W.: US20060094706 ( 2006).
173. Boyd, E., Brookfield, F., Georges, G., Goller, B., Huensch, S., Rueger, P., Rueth, M., Scheiblich, S., Schuell, C., Von Der, S.W., Warne, J., Weigand, S.: US20060089359 (2006).
174. Anderson, M., Keen, N.J., Pannifer, A.D.B., Pauptit, R.A., Rowsell, S.: US20060078975 (2006).
175. Mortlock, A.A.: US20060058523 (2006).
176. Mortlock, A.A.: US20060058325 (2006).
177. Mortlock, A.A., Jung, F.H.: US20060046987 (2006).
178. Geuns-meyer, S.D., Hodous, B.L., Chaffee, S.C., Tempest, P.A., Olivieri, P.R., Johnson, R.E., Albrecht, B.K., Patel, V.F.: US20060009453 (2006).
179. Carpinelli P, Moll J. Aurora kinase inhibitors: identification and preclinical validation of their biomarkers. Expert Opin Ther Targets 2008; 12: 69-80.
180. Li JJ, Li SA. Mitotic kinases: the key to duplication, segregation, and cytokinesis errors, chromosomal instability, and oncogenesis. Pharmacol Ther 2006; 111: 974-984.
181. Shen DW, Real FX, DeLeo AB, et al. Protein p53 and inducer-mediated erythroleukemia cell commitment to terminal cell division. Proc Natl Acad Sci USA 1983; 80: 5919-5922.
182. Vousden KH, Lu X. Live or let die: the cell's response to p53. Nat Rev Cancer 2002; 2: 594-604.
183. Mao JH, Wu D, Perez-Losada J, et al. Crosstalk between Aurora-A and p53: Frequent deletion or downregulation of Aurora-A in tumors from p53 null mice. Cancer Cell 2007; 11: 161-173.
184. Ouchi M, Fujiuchi N, Sasai K, et al. BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M transition. J Biol Chem 2004; 279: 19643-19648.
185. Toji S, Yabuta N, Hosomi T, et al. The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase. Genes Cells 2004; 9: 383-397.