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Expert Opinion on Investigational Drugs Volume 18, 2009 - Issue 4
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Reviews

Aurora kinase inhibitors in preclinical and clinical testing

Chun Hei Antonio Cheung Institute of Cancer Research, National Health Research Institutes, 2F, No. 367 Sheng Li Road, Tainan 704, Tainan, Taiwan, Republic of China; These authors contributed equally to this manuscript.
,
Mohane Selvaraj Coumar Division of Biotechnology & Pharmaceutical Research, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County, Taiwan, Republic of China For Hsing-Pang Hsieh; +886 37 246 166, ext. 35708; +886 37 586 456; [email protected] For Jang-Yang Chang; +886 6 7000123; +886 6 2083427; [email protected]; These authors contributed equally to this manuscript.
,
Hsing-Pang Hsieh Division of Biotechnology & Pharmaceutical Research, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County, Taiwan, Republic of China For Hsing-Pang Hsieh; +886 37 246 166, ext. 35708; +886 37 586 456; [email protected] For Jang-Yang Chang; +886 6 7000123; +886 6 2083427; [email protected]
&
Jang-Yang Chang Institute of Cancer Research, National Health Research Institutes, 2F, No. 367 Sheng Li Road, Tainan 704, Tainan, Taiwan, Republic of China
Pages 379-398 | Published online: 01 Apr 2009

Bibliography

  • Cheung CA, Coumar MS, Chang JY, Hsieh HP. Advances in aurora kinase inhibitor patents. Expert Opin Ther Patents 2009;19(3):321-56
  • Cancer: Key facts. July 2008. Available from: http://www.who.int/mediacentre/factsheets/fs297/en/index.html [Last accessed 1 August 2008]
  • Reddy GP, Tiarks CY, Pang L, et al. Cell cycle analysis and synchronization of pluripotent hematopoietic progenitor stem cells. Blood1997;90:2293-9
  • Xu X, Hamhouyia F, Thomas SD, et al. Inhibition of DNA replication and induction of S phase cell cycle arrest by G-rich oligonucleotides. J Biol Chem2001;276:43221-30
  • van der Meijden CM, Lapointe DS, Luong MX, et al. Gene profiling of cell cycle progression through S-phase reveals sequential expression of genes required for DNA replication and nucleosome assembly. Cancer Res2002;62:3233-43
  • Kline-Smith SL, Sandall S, Desai A. Kinetochore-spindle microtubule interactions during mitosis. Curr Opin Cell Biol2005;17:35-46
  • Kraft C, Herzog F, Gieffers C, et al. Mitotic regulation of the human anaphase-promoting complex by phosphorylation. EMBO J2003;22:6598-609
  • Fang G, Yu H, Kirschner MW. Control of mitotic transitions by the anaphase-promoting complex. Philos Trans R Soc Lond B Biol Sci1999;354:1583-90
  • Higuchi T, Uhlmann F. Stabilization of microtubule dynamics at anaphase onset promotes chromosome segregation. Nature2005;433:171-6
  • Rieder CL, Schultz A, Cole R, Sluder G. Anaphase onset in vertebrate somatic cells is controlled by a checkpoint that monitors sister kinetochore attachment to the spindle. J Cell Biol1994;127:1301-10
  • Wells WA, Murray AW. Aberrantly segregating centromeres activate the spindle assembly checkpoint in budding yeast. J Cell Biol1996;133:75-84
  • Jackson JR, Patrick DR, Dar MM, Huang PS. Targeted anti-mitotic therapies: can we improve on tubulin agents? Nat Rev Cancer2007;7:107-17
  • Smith SL, Bowers NL, Betticher DC, et al. Overexpression of Aurora B kinase (AURKB) in primary non-small cell lung carcinoma is frequent, generally driven from one allele, and correlates with the level of genetic instability. Br J Cancer2005;93:719-29
  • Zeng WF, Navaratne K, Prayson RA, Weil RJ. Aurora B expression correlates with aggressive behaviour in glioblastoma multiforme. J Clin Pathol2007;60:218-21
  • Dar AA, Zaika A, Piazuelo MB, et al. Frequent overexpression of aurora kinase A in upper gastrointestinal adenocarcinomas correlates with potent antiapoptotic functions. Cancer2008;112:1688-98
  • Reiter R, Gais P, Jutting U, et al. Aurora kinase A messenger RNA overexpression is correlated with tumor progression and shortened survival in head and neck squamous cell carcinoma. Clin Cancer Res2006;12:5136-41
  • Keen N, Taylor S. Aurora-kinase inhibitors as anticancer agents. Nat Rev Cancer2004;4:927-36
  • Fu J, Bian M, Jiang Q, Zhang C. Roles of Aurora kinases in mitosis and tumorigenesis. Mol Cancer Res2007;5:1-10
  • Agnese V, Bazan V, Fiorentino FP, et al. The role of Aurora-A inhibitors in cancer therapy. Ann Oncol2007;18(Suppl 6):vi47-52
  • Girdler F, Gascoigne KE, Eyers PA, et al. Validating Aurora B as an anti-cancer drug target. J Cell Sci2006;119:3664-75
  • Carpinelli P, Moll J. Aurora kinase inhibitors: identification and preclinical validation of their biomarkers. Expert Opin Ther Targets2008;12:69-80
  • Tanaka M, Ueda A, Kanamori H, et al. Cell-cycle-dependent regulation of human aurora A transcription is mediated by periodic repression of E4TF1. J Biol Chem2002;277:10719-26
  • Marumoto T, Hirota T, Morisaki T, et al. Roles of aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells. Genes Cells2002;7:1173-82
  • Hannak E, Kirkham M, Hyman AA, Oegema K. Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans. J Cell Biol2001;155:1109-16
  • Sugimoto K, Urano T, Zushi H, et al. Molecular dynamics of Aurora-A kinase in living mitotic cells simultaneously visualized with histone H3 and nuclear membrane protein importinalpha. Cell Struct Funct2002;27:457-67
  • 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 Chem2003;278:51786-95
  • Venoux M, Basbous J, Berthenet C, et al. ASAP is a novel substrate of the oncogenic mitotic kinase Aurora-A: phosphorylation on Ser625 is essential to spindle formation and mitosis. Hum Mol Genet2008;17:215-24
  • Kinoshita K, Noetzel TL, Pelletier L, et al. Aurora A phosphorylation of TACC3/maskin is required for centrosome-dependent microtubule assembly in mitosis. J Cell Biol2005;170:1047-55
  • De Luca M, Brunetto L, Asteriti IA, et al. Aurora-A and ch-TOG act in a common pathway in control of spindle pole integrity. Oncogene2008;27:6539-49
  • Conte N, Delaval B, Ginestier C, et al. TACC1-chTOG-Aurora A protein complex in breast cancer. Oncogene2003;22:8102-16
  • Liu Q, Kaneko S, Yang L, et al. Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215. J Biol Chem2004;279:52175-82
  • Katayama H, Sasai K, Kawai H, et al. Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet2004;36:55-62
  • Wang X, Zhou YX, Qiao W, et al. Overexpression of aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation. Oncogene2006;25:7148-58
  • Wang LH, Yan M, Xu DZ, et al. Requirement of aurora-A kinase in astral microtubule polymerization and spindle microtubule flux. Cell Cycle2008;7:1104-11
  • Liu Q, Ruderman JV. Aurora A, mitotic entry, and spindle bipolarity. Proc Natl Acad Sci USA2006;103:5811-16
  • Geddis AE, Kaushansky K. Megakaryocytes express functional Aurora-B kinase in endomitosis. Blood2004;104:1017-24
  • Bolton MA, Lan W, Powers SE, et al. Aurora B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation. Mol Biol Cell2002;13:3064-77
  • Yasui Y, Urano T, Kawajiri A, et al. Autophosphorylation of a newly identified site of Aurora-B is indispensable for cytokinesis. J Biol Chem2004;279:12997-3003
  • Hirano T, Kobayashi R, Hirano M. Condensins, chromosome condensation protein complexes containing XCAP-C, XCAP-E and a xenopus homolog of the Drosophila Barren protein. Cell1997;89:511-21
  • Hirano T, Mitchison TJ. A heterodimeric coiled-coil protein required for mitotic chromosome condensation in vitro. Cell1994;79:449-58
  • Takemoto A, Murayama A, Katano M, et al. Analysis of the role of Aurora B on the chromosomal targeting of condensin I. Nucleic Acids Res2007;35:2403-12
  • Emanuele MJ, Lan W, Jwa M, et al. Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly. J Cell Biol2008;181:241-54
  • Yokoyama T, Goto H, Izawa I, et al. Aurora-B and Rho-kinase/ROCK, the two cleavage furrow kinases, independently regulate the progression of cytokinesis: possible existence of a novel cleavage furrow kinase phosphorylates ezrin/radixin/moesin (ERM). Genes Cells2005;10:127-37
  • Yang Y, Wu F, Ward T, et al. Phosphorylation of HsMis13 by Aurora B kinase is essential for assembly of functional kinetochore. J Biol Chem2008;283:26726-36
  • Hirota T, Lipp JJ, Toh BH, Peters JM. Histone H3 serine 10 phosphorylation by Aurora B causes HP1 dissociation from heterochromatin. Nature2005;438:1176-80
  • Zeitlin SG, Shelby RD, Sullivan KF. CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in completion of cytokinesis. J Cell Biol2001;155:1147-57
  • Fischle W, Tseng BS, Dormann HL, et al. Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation. Nature2005;438:1116-22
  • Song J, Salek-Ardakani S, So T, Croft M. The kinases aurora B and mTOR regulate the G1-S cell cycle progression of T lymphocytes. Nat Immunol2007;8:64-73
  • Chen HL, Tang CJ, Chen CY, Tang TK. Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy. J Biomed Sci2005;12:297-310
  • Yan X, Cao L, Li Q, et al. Aurora C is directly associated with survivin and required for cytokinesis. Genes Cells2005;10:617-26
  • Kaori Sasai, 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 Cytoskeleton2004;59:249-63
  • Tang CJ, Lin CY, Tang TK. Dynamic localization and functional implications of Aurora-C kinase during male mouse meiosis. Dev Biol2006;290:398-410
  • Kimmins S, Crosio C, Kotaja N, et al. Differential functions of the Aurora-B and Aurora-C kinases in mammalian spermatogenesis. Mol Endocrinol2007;21:726-39
  • Wang XX, Liu R, Jin SQ, et al. Overexpression of Aurora-A kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line. Cell Res2006;16:356-66
  • Ulisse S, Delcros JG, Baldini E, et al. Expression of Aurora kinases in human thyroid carcinoma cell lines and tissues. Int J Cancer2006;119:275-82
  • Sorrentino R, Libertini S, Pallante PL, et al. Aurora B overexpression associates with the thyroid carcinoma undifferentiated phenotype and is required for thyroid carcinoma cell proliferation. J Clin Endocrinol Metab2005;90:928-35
  • Ikezoe T, Yang J, Nishioka C, et al. A novel treatment strategy targeting Aurora kinases in acute myelogenous leukemia. Mol Cancer Ther2007;6:1851-7
  • Ogawa E, Takenaka K, Katakura H, et al. Perimembrane Aurora-A expression is a significant prognostic factor in correlation with proliferative activity in non-small-cell lung cancer (NSCLC). Ann Surg Oncol2008;15:547-54
  • Nishida N, Nagasaka T, Kashiwagi K, et al. High copy amplification of the Aurora-A gene is associated with chromosomal instability phenotype in human colorectal cancers. Cancer Biol Ther2007;6:525-33
  • Lam AK, Ong K, Ho YH. Aurora kinase expression in colorectal adenocarcinoma: correlations with clinicopathological features, p16 expression and telomerase activity. Hum Pathol2008;39:599-604
  • 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 Med2004;10:262-7
  • Carter TA, Wodicka LM, Shah NP, et al. Inhibition of drug-resistant mutants of ABL, KIT and EGF receptor kinases. Proc Natl Acad Sci USA2005;102:11011-16
  • 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 T315I BCR-ABL mutation. Blood2007;109:500-2
  • Giles F, Cortes J, Bergstrom DA, et al. MK-0457, a Novel Multikinase inhibitor, is active in patients with chronic myeloid leukemia (CML) and acute lymphocytic leukemia (ALL) with the T315I BCR-ABL resistance mutation and patients with refractory JAK-2 Positive myeloproliferative diseases (MPD). ASH Annual Meeting Abstracts, 16 November 2006;108 [abstract 253]
  • Giles F, Freedman SJ, Xiao A, et al. MK-0457, a novel multikinase inhibitor, has activity in refractory AML, Including transformed JAK2 positive myeloproliferative disease (MPD), and in Philadelphia-positive ALL. ASH Annual Meeting Abstracts, 16 November 2006;108 [abstract 1967]
  • NCT00405054. A Phase II study of MK0457 in patients with T315I mutant CML and Ph+All. 14 December 2007. Available from: www.ClinicalTrials.gov [Last accessed 1 August 2008]
  • NCT00111683. A Phase I/II dose escalation study of MK0457 in patients with leukemia. 20 December 2007. Available from: www.ClinicalTrials.gov [Last accessed 1 August 2008]
  • NCT00500006. A Phase I dose escalation combination study in patients with CML and Ph+, ALL. 17 December 2007. Available from: www.ClinicalTrials.gov [Last accessed 1 August 2008]
  • 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 Res2007;13:3682-8
  • 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 Chem2007;50:2213-24
  • Tao Y, Zhang P, Girdler F, et al. Enhancement of radiation response in p53-deficient cancer cells by the Aurora-B kinase inhibitor AZD1152. Oncogene2008;27:3244-55
  • NCT00497731. AZD1152 in patients with advanced solid malignancies-study 1. 16 April 2008. Available from: www.ClinicalTrials.gov [Last accessed 2 December 2008]
  • Schellens JH, Boss D, Witteveen PO, et al. Phase I and pharmacological study of the novel aurora kinase inhibitor AZD1152. [Meeting Abstracts]. J Clin Oncol2006;24(18 Suppl):3008
  • NCT00530699. Safety, tolerability and PK of AZD1152 in patients with relapsed acute myeloid leukaemia (AML). 3 January 2008. Available from: www.ClinicalTrials.gov [Last accessed 1 August 2008]
  • Fancelli D, Moll J, Varasi M, et al. 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent Aurora kinase inhibitor with a favorable antitumor kinase inhibition profile. J Med Chem2006;49:7247-51
  • 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 Ther2007;6:3158-68
  • 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 T315I. Blood2008;111:4355-64
  • Cohen RB, Jones SF, von Mehren M, et al. Phase I study of the pan aurora kinases (AKs) inhibitor PHA-739358 administered as a 24 h infusion without/with G-CSF in a 14-day cycle in patients with advanced solid tumors.[Meeting Abstracts] J Clin Oncol2008;26
  • Bernard A, Jurgen M, Fabrina, B, Silvia C. A method of administering an antitumor compound. WO08052931A1 (2008)
  • NCT00335868. PHA-739358 in treating patients with chronic myelogenous leukemia that relapsed after imatinib mesylate or c-ABL therapy. 23 May 2008. Available from: www.ClinicalTrials.gov [Last accessed 1 August 2008]
  • NCT00766324. PHA-739358 for treatment of hormone refractory prostate cancer. 2 October 2008. Available from: www.ClinicalTrials.gov [Last accessed 1 August 2008]
  • 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 USA2007;104:4106-11
  • 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 Biol2007;27:4513-25
  • Jones SF, Cohen RB, Dees EC, et al. Phase I clinical trial of MLN8054, a selective inhibitor of Aurora A kinase.[Meeting Abstracts] J Clin Oncol2007;25(18 Suppl):3577
  • NCT00249301. A Study of MLN8054 in patients with advanced solid tumors. 28 March 2008. Available from: www.ClinicalTrials.gov [Last accessed 1 August 2008]
  • NCT00652158. A Phase 1 trial of extended MLN8054 dosing in patients with advanced malignancies. 9 April 2008. Available from: www.ClinicalTrials.gov [Last accessed 1 August 2008]
  • Sells T, Ecsedy JA, Stroud SG, et al. MLN8237: an orally active small molecule inhibitor of Aurora A kinase in Phase I clinical trials. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • Chakravarty A, Yu L, Huck J, et al. Pharmacodynamics/pharmacokinetic/efficacy relationships of MLN8237, a small molecule inhibitor of Aurora A kinase. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • Nawrocki ST, Medina E, Smith S, et al. The Aurora kinase inhibitor MLN8237 has potent anticancer activity in CML and Ph+ ALL models and significantly increases the efficacy of nilotinib. ASH Annual Meeting (Meeting Abstract); 12–16 April 2008, San Francisco, CA, USA
  • NCT00500903. A study of MLN8237, a novel Aurora A kinase inhibitor, in patients with advanced solid tumors. Available from: www.ClincialTrials.gov [Last accessed 1 August 2008]
  • NCT00697346. Study of MLN8237 in patients with advanced hematological malignancies. Available from: www.ClinicalTrials.gov [Last accessed 1 August 2008]
  • Griffiths G, Scaerou F, Sorrell D, et al. Anti-tumor activity of CYC116, a novel small molecule inhibition of Aurora kinases and VEGFR2. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • Hajduch M, Vydra P, Dzubak P, et al. In vivo mode of action of CYC116, a novel small molecule inhibitor of Aurora kinases and VEGFR2. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • MacCallum D, Green S. Combined anticancer pyrimidine-thiazole aurora kinase inhibitors. WO07132221A1 (2007)
  • MacCallum D, Melville J, Watt K, Green SR. Combination studies with the oral Aurora kinase inhibitor CYC116 and chemotherapeutic agents. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • Fernandez E, Hardy A, Orrell D, et al. Optimal cancer chronotherapeutic schedules of Seliciclib revealed by a system biology approach. ACCR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • Chassagnole C, Fernandez E, Scaerou F, et al. System biology analysis of CYC116, a novel aurora kinase inhibitor. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • NCT00560716. A Phase I pharmacologic study of CYC116, an oral aurora kinase inhibitor, in patients with advanced solid tumors. 16 November 2007. Available from: www.ClinicalTrials.gov [Last accessed 1 August 2008]
  • NCT00530465. CYC116 in treating patients with advanced solid tumors. 23 May 2008. Available from: www.ClinicalTrials.gov [Last accessed 1 August 2008]
  • Oslob JD, Romanowski MJ, Allen DA, et al. Discovery of a potent and selective Aurora kinase inhibitor. Bioorg Med Chem Lett2008;18:4880-4
  • Gamo K, Belmont B, Tangonan B, et al. SNS-314, a novel small-molecule Aurora kinase inhibitor, induces cell-cycle defects and potently supresses tumor growth. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • Evachik M, Hogan J, Arbitrario J, et al. SNS-314, a potent inhibitor of aurora kinases, has preclinical anti-tumour activity and induces apoptosis. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • Hogan J, Kumer J, Arbitrario J, et al. SNS-314, a potent inhibitor of aurora kinases, shows broad anti-tumor activity and dosing flexibility in vivo. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • Robert F, Hurwitz H, Verschraegen CF, et al. Phase 1 trial of SNS-314, a novel selective inhibitor of aurora kinases A, B, and C, in advanced solid tumor patients. ASCO Annual Meeting (Meeting Abstracts); 30 May–3 June 2008, Chicago, IL, USA
  • NCT0051966;2. Safety and tolerability study of SNS-314 for advanced solid tumors. 12 June 2008. Available from: www.ClinicalTrials.gov [Last accessed 1 August 2008]
  • Yang J, Anderson K, Hardwicke MA, et al. Biochemical characterization of GSK1070916, a potent and selective inhibitor of Aurora B kinase with extremely AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • Hardwicke MA, Liao Q, Plant R, et al. Biological characterization of GSK1070916: a potent and selective inhibitor of Aurora B/C kinase. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • Sutton D, Diamond M, Liu Q, et al. GSK1070916A, a potent and selective Aurora-B kinase inhibitor, has broad spectrum activity against human tumor xenografts in nude mice. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • Bhattacharya S, Wishka D, Luzzio M, et al. SAR and chemistry of Aurora kinase inhibitors: discovery of PF-3814735, an oral clinical candidate. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • Jani J, Jakubczak J, Arcari J, et al. Identification and characterization of PF-03814735, an oral aurora inhibitor for cancer therapy. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • Jones SF, Burris HA, Dumez H, et al. Phase I accelerated dose-escalation, pharmacokinetic (PK) and pharmacodynamic study of PF-03814735, an oral aurora kinase inhibitor, in patients with advanced solid tumors: preliminary results. ASCO Annual Meeting (Meeting Abstracts); 30 May–3 June 2008, Chicago, IL, USA
  • Bray MR. ENMD-981693: an oral, aurora kinase-angiogenesis inhibitor. Drug Discovery and Development of Innovative Therapeutics (Meeting Abstracts); 6–9 August 2007, Boston, MA, USA
  • Bray MR. ENMD-2076, an oral Aurora A and angiogenesis kinase inhibitor. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • NCT00658671. A dose-escalation study of ENMD-2076; administered orally to patients with advanced cancer. 9 July 2008. Available from: www.ClinicalTrials.gov [Last accessed 1 August 2008]
  • Howard S, Berdini V, Boulstridge JA, et al. Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. J Med Chem2009;52(2):379-88
  • Tanaka R, Squires M, Kimura S, et al. Activity of the multi-targeted kinase inhibitor, AT9283 on Imatinib-resistant CML models. ASH Annual Meeting (Meeting abstract); 12–16 April 2008, San Francisco, CA, USA
  • NCT00443976. Aurora kinase inhibitor AT9283 in treating patients with advanced or metastatic solid tumors or non-Hodgkin's lymphoma. 23 July 2008. Available from: www.ClinicalTrials.gov [Last accessed 30 December 2008]
  • NCT00522990. Study to assess the safety of escalating doses of AT9283, in Patients with leukemias. 23 April 2008. Available from: www.ClinicalTrials.gov [Last accessed 30 December 2008]
  • Plummer ER, Calvert H, Arkenau H, et al. A dose-escalation and pharmacodynamic study of AT9283 in patients with refractory solid tumours. J Clin Oncol (Meeting Abstracts) 2008;26(15 Suppl):2519
  • Foran JM, Ravandi F, O'brien SM, et al. Phase I and pharmacodynamic trial of AT9283, an aurora kinase inhibitor, in patients with refractory leukemia. ASCO Annual Meeting (Meeting Abstracts); 30 May–3 June 2008, Chicago, IL, USA
  • Aissat N, Serova M, Ghoul A, et al. Cellular and molecular mechanisms of action of AS703569, a novel aurora kinase inhibitor, in human cancer cell lines. AACR-NCI-EORTC International Conference (Meeting Abstract), 22 – 26 October 2007, San Francisco, CA, USA
  • Serova M, Aissat N, Ghoul A, et al. AS703569, a novel aurora kinase inhibitor, enhances the antiproliferative effects of other targeted therapies in human cancer cell lines. AACR-NCI-EORTC International Conference (Meeting Abstract), 22 - 26 October 2007, San Francisco, CA, USA
  • Renshaw JS, Patnaik A, Gordon M, et al. A phase I two arm trial of AS703569 (R763), an orally available aurora kinase inhibitor, in subjects with solid tumors: preliminary results. ASCO Annual Meeting (Meeting Abstracts); 30 May–3 June 2007, Chicago, IL, USA
  • NCT00543387. Treatment of patients with advanced and/or refractory solid tumors. 5 November 2008. Available from: www.ClinicalTrials.gov [Last accessed 1 August 2008]
  • Clifford A, Grand C, Vankayalapati H, et al. Discovery and development of MP529, a new effective and selective inhibitor of aurora A kinase. AACR Annual Meeting (Meeting Abstracts); 14–18 April 2007, Los Angeles, CA, USA
  • 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 Ther2006;5:1764-73
  • Joshi-Hangal R, Tang C, Sadikin S, et al. Pharmacokinetics of MP529, a selective Aurora A kinase inhibitor, in a novel subcutaneous delivery system. AACR Annual Meeting (Meeting Abstracts); 12–16 April 2008, San Francisco, CA, USA
  • Lin R, Connolly PJ, Huang S, et al. 1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities. J Med Chem2005;48:4208-11
  • 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 Res2005;65:9038-46
  • 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 Chem2005;48:3080-4
  • Soncini C, Carpinelli P, Gianellini L, et al. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Res2006;12:4080-9
  • Walter R, Heckel A, Roth G, et al. Substituted indolinones, preparation thereof and their use as pharmaceutical compositions. US6638965 (2003)
  • 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 Biol2003;161:281-94
  • Kurihara D, Matsunaga S, Kawabe A, et al. Aurora kinase is required for chromosome segregation in tobacco BY-2 cells. Plant J2006;48:572-80
  • Sessa F, Mapelli M, Ciferri C, et al. Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Mol Cell2005;18:379-91
  • 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 Sci2007;120:1245-55
  • Heron NM, Anderson M, Blowers DP, et al. SAR and inhibitor complex structure determination of a novel class of potent and specific Aurora kinase inhibitors. Bioorg Med Chem Lett2006;16:1320-3
  • CHR-3520: potent Aurora/multi-kinase inhibitor. Available from: http://www.chromatherapeutics.com/Aurora-Kinase_backup.htm [Last accessed 16 December 2008]
  • Vader G, Lens SM. The Aurora kinase family in cell division and cancer. Biochim Biophys Acta2008;1786:60-72
  • Gautschi O, Heighway J, Mack PC, et al. Aurora kinases as anticancer drug targets. Clin Cancer Res2008;14:1639-48
  • Girdler F, Sessa F, Patercoli S, et al. Molecular basis of drug resistance in aurora kinases. Chem Biol2008;15:552-62
  • Lin YG, Immaneni A, Merritt WM, et al. Targeting aurora kinase with MK-0457 inhibits ovarian cancer growth. Clin Cancer Res2008;14:5437-46

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