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Drug Evaluations

ENMD-2076 for hematological malignancies

& , MDCM FRCP(C)
Pages 717-732 | Published online: 08 Mar 2012

Bibliography

  • Carmena M, Earnshaw WC. The cellular geography of aurora kinases. Nat Rev Mol Cell Biol 2003;4:842-54
  • Kimura M, Kotani S, Hattori T, Cell cycle-dependent expression and spindle pole localization of a novel human protein kinase, Aik, related to Aurora of Drosophila and yeast Ipl1. J Biol Chem 1997;272:13766-71
  • Bischoff JR, Anderson L, Zhu Y, A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. Embo J 1998;17:3052-65
  • Zhou H, Kuang J, Zhong L, Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet 1998;20:189-93
  • Barr AR, Gergely F. Aurora-A: the maker and breaker of spindle poles. J Cell Sci 2007;120:2987-96
  • Honda K, Mihara H, Kato Y, Degradation of human Aurora2 protein kinase by the anaphase-promoting complex-ubiquitin-proteasome pathway. Oncogene 2000;19:2812-19
  • Taguchi S, Honda K, Sugiura K, Degradation of human Aurora-A protein kinase is mediated by hCdh1. FEBS Lett 2002;519:59-65
  • Lindon C, Pines J. Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells. J Cell Biol 2004;164:233-41
  • Fu J, Bian M, Jiang Q, Zhang C. Roles of Aurora kinases in mitosis and tumorigenesis. Mol Cancer Res 2007;5:1-10
  • Liu Q, Kaneko S, Yang L, Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215. J Biol Chem 2004;279:52175-82
  • Lens SM, Voest EE, Medema RH. Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat Rev Cancer 2010;10:825-41
  • Manfredi MG, Ecsedy JA, Meetze KA, Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase. Proc Natl Acad Sci USA 2007;104:4106-11
  • Lu LY, Wood JL, Ye L, Aurora A is essential for early embryonic development and tumor suppression. J Biol Chem 2008;283:31785-90
  • Sasai K, Parant JM, Brandt ME, Targeted disruption of Aurora A causes abnormal mitotic spindle assembly, chromosome misalignment and embryonic lethality. Oncogene 2008;27:4122-7
  • Cowley DO, Rivera-Perez JA, Schliekelman M, Aurora-A kinase is essential for bipolar spindle formation and early development. Mol Cell Biol 2009;29:1059-71
  • Cross SM, Sanchez CA, Morgan CA, A p53-dependent mouse spindle checkpoint. Science 1995;267:1353-6
  • Yu X, Minter-Dykhouse K, Malureanu L, Chfr is required for tumor suppression and Aurora A regulation. Nat Genet 2005;37:401-6
  • Fu Z, Regan K, Zhang L, Deficiencies in Chfr and Mlh1 synergistically enhance tumor susceptibility in mice. J Clin Invest 2009;119:2714-24
  • Mao JH, Wu D, Perez-Losada J, Crosstalk between Aurora-A and p53: frequent deletion or downregulation of Aurora-A in tumors from p53 null mice. Cancer Cell 2007;11:161-73
  • Carmena M, Ruchaud S, Earnshaw WC. Making the Auroras glow: regulation of Aurora A and B kinase function by interacting proteins. Curr Opin Cell Biol 2009;21:796-805
  • Carvajal RD, Tse A, Schwartz GK. Aurora kinases: new targets for cancer therapy. Clin Cancer Res 2006;12:6869-75
  • Lin YS, Su LJ, Yu CT, Gene expression profiles of the aurora family kinases. Gene Expr 2006;13:15-26
  • Bernard M, Sanseau P, Henry C, Cloning of STK13, a third human protein kinase related to Drosophila aurora and budding yeast Ipl1 that maps on chromosome 19q13.3-ter. Genomics 1998;53:406-9
  • Yang KT, Li SK, Chang CC, Aurora-C kinase deficiency causes cytokinesis failure in meiosis I and production of large polyploid oocytes in mice. Mol Biol Cell 2010;21:2371-83
  • Tseng TC, Chen SH, Hsu YP, Tang TK. Protein kinase profile of sperm and eggs: cloning and characterization of two novel testis-specific protein kinases (AIE1, AIE2) related to yeast and fly chromosome segregation regulators. DNA Cell Biol 1998;17:823-33
  • Kimmins S, Crosio C, Kotaja N, Differential functions of the Aurora-B and Aurora-C kinases in mammalian spermatogenesis. Mol Endocrinol 2007;21:726-39
  • Dieterich K, Soto Rifo R, Faure AK, Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility. Nat Genet 2007;39:661-5
  • Dieterich K, Zouari R, Harbuz R, The Aurora Kinase C c.144delC mutation causes meiosis I arrest in men and is frequent in the North African population. Hum Mol Genet 2009;18:1301-9
  • Slattery SD, Mancini MA, Brinkley BR, Hall RM. Aurora-C kinase supports mitotic progression in the absence of Aurora-B. Cell Cycle 2009;8:2984-94
  • Sasai K, Katayama H, Stenoien DL, Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells. Cell Motil Cytoskeleton 2004;59:249-63
  • Ikezoe T, Yang J, Nishioka C, A novel treatment strategy targeting Aurora kinases in acute myelogenous leukemia. Mol Cancer Ther 2007;6:1851-7
  • Kobayashi M, Nakamura S, Ono T, Analysis of Aurora kinase expressions and cell cycle regulation by Aurora-C in leukemia cells. Blood 2006;108
  • Ochi T, Fujiwara H, Suemori K, Aurora-A kinase: a novel target of cellular immunotherapy for leukemia. Blood 2009;113:66-74
  • Ye D, Garcia-Manero G, Kantarjian HM, Analysis of Aurora kinase a expression in CD34(+) blast cells isolated from patients with myelodysplastic syndromes and acute myeloid leukemia. J Hematop 2009;2:2-8
  • Lucena-Araujo AR, de Oliveira FM, Leite-Cueva SD, High expression of AURKA and AURKB is associated with unfavorable cytogenetic abnormalities and high white blood cell count in patients with acute myeloid leukemia. Leuk Res 2011;35:260-4
  • Inamdar KV, O'Brien S, Sen S, Aurora-A kinase nuclear expression in chronic lymphocytic leukemia. Mod Pathol 2008;21:1428-35
  • Harrington EA, Bebbington D, Moore J, VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med 2004;10:262-7
  • Huang XF, Luo SK, Xu J, Aurora kinase inhibitory VX-680 increases Bax/Bcl-2 ratio and induces apoptosis in Aurora-A-high acute myeloid leukemia. Blood 2008;111:2854-65
  • McLaughlin J, Markovtsov V, Li H, Preclinical characterization of Aurora kinase inhibitor R763/AS703569 identified through an image-based phenotypic screen. J Cancer Res Clin Oncol 2010;136:99-113
  • Ikezoe T, Yang J, Nishioka C, Yokoyama A. p53 is critical for the Aurora B kinase inhibitor-mediated apoptosis in acute myelogenous leukemia cells. Int J Hematol 2010;91:69-77
  • Yang J, Ikezoe T, Nishioka C, 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;110:2034-40
  • Oke A, Pearce D, Wilkinson RW, AZD1152 rapidly and negatively affects the growth and survival of human acute myeloid leukemia cells in vitro and in vivo. Cancer Res 2009;69:4150-8
  • Walsby E, Walsh V, Pepper C, Effects of the aurora kinase inhibitors AZD1152-HQPA and ZM447439 on growth arrest and polyploidy in acute myeloid leukemia cell lines and primary blasts. Haematologica 2008;93:662-9
  • Hardwicke MA, Oleykowski CA, Plant R, GSK1070916, a potent Aurora B/C kinase inhibitor with broad antitumor activity in tissue culture cells and human tumor xenograft models. Mol Cancer Ther 2009;8:1808-17
  • Pratz KW, Cortes J, Roboz GJ, A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood 2009;113:3938-46
  • Shiotsu Y, Kiyoi H, Ishikawa Y, KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood 2009;114:1607-17
  • Kojima K, Konopleva M, Tsao T, Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent postmitotic checkpoints and synergistically induces p53-mediated mitochondrial apoptosis along with reduced endoreduplication in acute myelogenous leukemia. Blood 2008;112:2886-95
  • Grundy M, Seedhouse C, Shang S, The FLT3 internal tandem duplication mutation is a secondary target of the aurora B kinase inhibitor AZD1152-HQPA in acute myelogenous leukemia cells. Mol Cancer Ther 2010;9:661-72
  • Tanaka R, Squires MS, Kimura S, Activity of the multitargeted kinase inhibitor, AT9283, in imatinib-resistant BCR-ABL-positive leukemic cells. Blood 2010;116:2089-95
  • Kelly KR, Ecsedy J, Medina E, The novel Aurora A kinase inhibitor MLN8237 is active in resistant chronic myeloid leukaemia and significantly increases the efficacy of nilotinib. J Cell Mol Med 2011;15:2057-70
  • Donato NJ, Fang D, Sun H, Targets and effectors of the cellular response to aurora kinase inhibitor MK-0457 (VX-680) in imatinib sensitive and resistant chronic myelogenous leukemia. Biochem Pharmacol 2010;79:688-97
  • Okabe S, Tauchi T, Ohyashiki JH, Ohyashiki K. Mechanism of MK-0457 efficacy against BCR-ABL positive leukemia cells. Biochem Biophys Res Commun 2009;380:775-9
  • Gontarewicz A, Balabanov S, Keller G, PHA-680626 exhibits anti-proliferative and pro-apoptotic activity on Imatinib-resistant chronic myeloid leukemia cell lines and primary CD34+ cells by inhibition of both Bcr-Abl tyrosine kinase and Aurora kinases. Leuk Res 2008;32:1857-65
  • Gontarewicz A, Balabanov S, Keller G, 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. Blood 2008;111:4355-64
  • Fei F, Stoddart S, Groffen J, Heisterkamp N. Activity of the Aurora kinase inhibitor VX-680 against Bcr/Abl-positive acute lymphoblastic leukemias. Mol Cancer Ther 2010;9:1318-27
  • Grundy M, Seedhouse C, Russell NH, Pallis M. P-glycoprotein and breast cancer resistance protein in acute myeloid leukaemia cells treated with the aurora-B kinase inhibitor barasertib-hQPA. BMC Cancer 2011;11:254
  • Dai Y, Chen S, Venditti CA, Vorinostat synergistically potentiates MK-0457 lethality in chronic myelogenous leukemia cells sensitive and resistant to imatinib mesylate. Blood 2008;112:793-804
  • Okabe S, Tauchi T, Ohyashiki K. Efficacy of MK-0457 and in combination with vorinostat against Philadelphia chromosome positive acute lymphoblastic leukemia cells. Ann Hematol 2010;89:1081-7
  • Fiskus W, Wang Y, Joshi R, Cotreatment with vorinostat enhances activity of MK-0457 (VX-680) against acute and chronic myelogenous leukemia cells. Clin Cancer Res 2008;14:6106-15
  • Cheong JW, Jung HI, Eom JI, Aurora-A kinase inhibition enhances the cytosine arabinoside-induced cell death in leukemia cells through apoptosis and mitotic catastrophe. Cancer Lett 2010;297:171-81
  • Yakushijin Y, Hamada M, Yasukawa M. The expression of the aurora-A gene and its significance with tumorgenesis in non-Hodgkin's lymphoma. Leuk Lymphoma 2004;45:1741-6
  • Hamada M, Yakushijin Y, Ohtsuka M, Aurora2/BTAK/STK15 is involved in cell cycle checkpoint and cell survival of aggressive non-Hodgkin's lymphoma. Br J Haematol 2003;121:439-47
  • Camacho E, Bea S, Salaverria I, Analysis of Aurora-A and hMPS1 mitotic kinases in mantle cell lymphoma. Int J Cancer 2006;118:357-63
  • den Hollander J, Rimpi S, Doherty JR, Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state. Blood 2010;116:1498-505
  • Iqbal J, Weisenburger DD, Chowdhury A, Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic gammadelta T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro. Leukemia 2011;25:348-58
  • Sander B, Flygare J, Porwit-Macdonald A, Mantle cell lymphomas with low levels of cyclin D1 long mRNA transcripts are highly proliferative and can be discriminated by elevated cyclin A2 and cyclin B1. Int J Cancer 2005;117:418-30
  • Mori N, Ishikawa C, Senba M, Effects of AZD1152, a selective Aurora B kinase inhibitor, on Burkitt's and Hodgkin's lymphomas. Biochem Pharmacol 2011;81:1106-15
  • Ikezoe T, Takeuchi T, Yang J, Analysis of Aurora B kinase in non-Hodgkin lymphoma. Lab Invest 2009;89:1364-73
  • Yang D, Liu H, Goga A, Therapeutic potential of a synthetic lethal interaction between the MYC proto-oncogene and inhibition of aurora-B kinase. Proc Natl Acad Sci USA 2010;107:13836-41
  • Goga A, Yang D, Tward AD, Inhibition of CDK1 as a potential therapy for tumors over-expressing MYC. Nat Med 2007;13:820-7
  • Hoglund A, Nilsson LM, Forshell LP, Myc sensitizes p53-deficient cancer cells to the DNA-damaging effects of the DNA methyltransferase inhibitor decitabine. Blood 2009;113:4281-8
  • Qi W, Liu X, Cooke LS, AT9283, a novel aurora kinase inhibitor, suppresses tumor growth in aggressive B-cell lymphomas. Int J Cancer 2011; Epub ahead of print
  • Qi W, Cooke LS, Liu X, Aurora inhibitor MLN8237 in combination with docetaxel enhances apoptosis and anti-tumor activity in mantle cell lymphoma. Biochem Pharmacol 2011;81:881-90
  • Chng WJ, Ahmann GJ, Henderson K, Clinical implication of centrosome amplification in plasma cell neoplasm. Blood 2006;107:3669-75
  • Chng WJ, Braggio E, Mulligan G, 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;111:1603-9
  • Hose D, Reme T, Meissner T, Inhibition of aurora kinases for tailored risk-adapted treatment of multiple myeloma. Blood 2009;113:4331-40
  • Hose D, Reme T, Hielscher T, Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma. Haematologica 2011;96:87-95
  • Evans RP, Naber C, Steffler T, The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma. Br J Haematol 2008;140:295-302
  • Shi Y, Reiman T, Li W, Targeting aurora kinases as therapy in multiple myeloma. Blood 2007;109:3915-21
  • Santo L, Hideshima T, Cirstea D, Antimyeloma activity of a multitargeted kinase inhibitor, AT9283, via potent Aurora kinase and STAT3 inhibition either alone or in combination with lenalidomide. Clin Cancer Res 2011;17:3259-71
  • Gorgun G, Calabrese E, Hideshima T, A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma. Blood 2010;115:5202-13
  • Negri JM, McMillin DW, Delmore J, In vitro anti-myeloma activity of the Aurora kinase inhibitor VE-465. Br J Haematol 2009;147:672-6
  • Evans R, Naber C, Steffler T, Aurora A kinase RNAi and small molecule inhibition of Aurora kinases with VE-465 induce apoptotic death in multiple myeloma cells. Leuk Lymphoma 2008;49:559-69
  • Wang X, Sinn AL, Pollok K, Preclinical activity of a novel multiple tyrosine kinase and aurora kinase inhibitor, ENMD-2076, against multiple myeloma. Br J Haematol 2010;150:313-25
  • Wang X, Sinn AL, Suvannasankha A, The novel Aurora kinase inhibitor ENMD-2076 has potent single agent activity against multiple myeloma (MM) in vitro and in vivo, and shows synergistic activity in combination with lenalidomide. Blood 2008;112
  • Yoshida A, Zokumasu K, Yamauchi T, Marked upregulations of survivin and aurora-B kinase are associated with disease progression in the myelodysplastic syndromes. Blood 2011;118: 1633
  • Dawson MA, Curry JE, Barber K, AT9283, a potent inhibitor of the Aurora kinases and Jak2, has therapeutic potential in myeloproliferative disorders. Br J Haematol 2010;150:46-57
  • Coumar MS, Cheung CH, Chang JY, Hsieh HP. Advances in Aurora kinase inhibitor patents. Expert Opin Ther Patent 2009;19:321-56
  • Fletcher GC, Brokx RD, Denny TA, ENMD-2076 is an orally active kinase inhibitor with antiangiogenic and antiproliferative mechanisms of action. Mol Cancer Ther 2011;10:126-37
  • Tentler JJ, Bradshaw-Pierce EL, Serkova NJ, Assessment of the in vivo antitumor effects of ENMD-2076, a novel multitargeted kinase inhibitor, against primary and cell line-derived human colorectal cancer xenograft models. Clin Cancer Res 2010;16:2989-98
  • Hembrough TA, Chen X, Burke PA, Inhibition of multiple myeloma tumor growth and FGFR3 by the Aurora-angiogenesis inhibitor ENMD-981693. Blood 2007;110: 366a
  • Fletcher GC, Brokx RD, Denny TA, ENMD-2076 Is an Orally-Active Kinase Inhibitor with Antiangiogenic and Antiproliferative Mechanisms of Action. Mol Cancer Ther 2010
  • Diamond JR, Bastos BR, Hansen RJ, Phase I safety, pharmacokinetic, and pharmacodynamic study of ENMD-2076, a novel angiogenic and Aurora kinase inhibitor, in patients with advanced solid tumors. Clin Cancer Res 2011;17:849-60
  • Yee KWL, Chen H-WT, Brandwein J, A phase I study of ENMD-2076 in patients with relapsed or refractory leukemia. Blood 2010;116: 1355
  • Farag S, Zhang S, Suvannasankha A, Clinical activity of a novel multiple tyrosine kinase and Aurora kinase inhibitor, ENMD-2076, against multiple myeloma: Interim phase I trial results. Blood 2010;116: 816
  • Matulonis U, Tew WP, Matei D, A phase II study of ENMD-2076 in platinum-resistant ovarian cancer. J Clin Oncol 2011;29: 3375
  • Pollard JR, Mortimore M. Discovery and development of aurora kinase inhibitors as anticancer agents. J Med Chem 2009;52:2629-51
  • Hook KE, Garza SJ, Lira ME, An integrated genomic approach to identify predictive biomarkers of response to the Aurora kinase inhibitor PF-03814735. Mol Cancer Ther 2012; Epub ahead of print
  • Chowdhury A, Chowdhury S, Tsai MY. A novel Aurora kinase A inhibitor MK-8745 predicts TPX2 as a therapeutic biomarker in non-Hodgkin lymphoma cell lines. Leuk Lymphoma 2011; Epub ahead of print
  • Renshaw JS, Patnaik A, Gordon M, A phase I two arm trial of AS703569 (R763), an orally available aurora kinase inhibitor, in subjects with solid tumors: preliminary results. J Clin Oncol 2007;25: 6225
  • Sonet A, Graux C, Maertens J, Phase I, dose-escalation study of 2 dosing regimens of AS703569, an Inhibitor of Aurora and other kinases, administered orally in patients with advanced hematological malignancies. Blood 2008;112: 1018
  • AS703569 and gemcitabine combination in advanced malignancies. ClinicalTrialsgov 2010. Available from: http://clinicaltrials.gov/show/NCT01097512 [Cited 11 November 2010]
  • Howard S, Berdini V, Boulstridge JA, Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. J Med Chem 2009;52:379-88
  • Foran JM, Ravandi F, O'Brien SM, Phase I and pharmacodynamic trial of AT9283, an aurora kinase inhibitor, in patients with refractory leukemia. J Clin Oncol 2008;26: 1165
  • Arkenau HT, Plummer R, Molife LR, A phase I dose escalation study of AT9283, a small molecule inhibitor of aurora kinases, in patients with advanced solid malignancies. Ann Oncol 2011 [Epub a head print]
  • Foote KM, Mortlock AA, Heron NM, The discovery of AZD1152: a novel and highly potent aurora kinase. Proceedings of the American Association for Cancer Research-National Cancer Institute-European Organization for Research and Treatment of Cancer, Molecular Targets and Therapeutics; 2005. p. 267
  • Boss DS, Witteveen PO, van der Sar J, Clinical evaluation of AZD1152, an i.v. inhibitor of Aurora B kinase, in patients with solid malignant tumors. Ann Oncol 2011;22:431-7
  • Lowenberg B, Muus P, Ossenkoppele G, Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia. Blood 2011;118:6030-6
  • Study to assess the safety and tolerability of AZD1152 in combination with low dose cytosine arabinoside (LDAC). ClinicalTrialsgov 2009. Available from: http://clinicaltrials.gov/show/NCT00926731 [Cited 11 November 2010]
  • Study to investigate the efficacy, safety and tolerability of AZD1152 alone and in combination with low dose cytosine arabinoside (LDAC) in acute myeloid leukaemia (AML) patients (SPARK-AML1). ClinicalTrialsgov 2009. Available from: http://clinicaltrials.gov/show/NCT00952588 [Cited 11 November 2010]
  • An open label, single centre mass balance C14 study in patients with acute myeloid leukaemia (AML). ClinicalTrialsgov 2009. Available from: http://clinicaltrials.gov/show/NCT01019161 [Cited 11 November 2010]
  • Kantarjian HM, Sekeres MA, Ribrag V, Phase I study to assess the safety and tolerability of AZD1152 in combination with low dose cytosine arabinoside in patients with acute myeloid leukemia (AML). Blood 2010;116: 287
  • Keen N, Brown E, Crafter C, Biological characterisation of AZD1152, a highly potent and selective inhibitor of aurora kinase activity. Proceedings of the American Association for Cancer Research-National Cancer Institute-European Organization for Research and Treatment of Cancer, Molecular Targets and Therapeutics; 2005. p. 183
  • Gurtler U, Tontsch-Grunt U, Jarvis M, Effect of BI 811283, a novel inhibitor of Aurora B kinase, on tumor senescence and apoptosis. J Clin Oncol 2010;28: e13632
  • Mross KB, Scheulen ME, Frost A, A phase I dose-escalation study of BI 811283, an Aurora B inhibitor, administered every three weeks in patients with advanced solid tumors. J Clin Oncol 2010;28: 235s
  • Scheulen ME, Mross KB, Richly H, A phase I dose-escalation study of BI 811283, an Aurora B inhibitor, administered days 1 and 15, every four weeks in patients with advanced solid tumors. J Clin Oncol 2010;28: e13065
  • Hajduch M, Vydra D, Dzubak P, In vivo mode of action of CYC116, a novel small molecule inhibitor of Aurora kinases and VEGFR2. Proceedings of the 99th Annual Meeting of the American Association for Cancer Research; 2008: abstract 5645
  • A phase I pharmacologic study of CYC116, an oral Aurora kinase inhibitor, in patients with advanced solid tumors. ClinicalTrialsgov 2007. Available from: http://clinicaltrials.gov/ct2/show/NCT00560716 [Cited 9 January 2011]
  • Fancelli D, Moll J, Varasi M, 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 Chem 2006;49:7247-51
  • Cohen RB, Jones SF, Aggarwal C, A phase I dose-escalation study of danusertib (PHA-739358) administered as a 24-hour infusion with and without granulocyte colony-stimulating factor in a 14-day cycle in patients with advanced solid tumors. Clin Cancer Res 2009;15:6694-701
  • Cortes-Franco J, Dombret H, Schafhausen P, Danusertib hydrochloride (PHA-739358), a multi-Kinase Aurora inhibitor, elicits clinical benefit in advanced chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia. Blood 2009;114
  • Laffranchi B, De Jonge MJ, Bajetta E, Phase II study of danusertib (D) in advanced/metastatic colorectal and pancreatic cancers (CRC, PC). J Clin Oncol 2010;28: 13558
  • Rosen PJ, Tolcher AW, Lee P, Phase I study of danusertib (D) in combination with bevacizumab (B) in solid tumors. J Clin Oncol 2010;28: 249s
  • Steeghs N, Eskens FA, Gelderblom H, Phase I pharmacokinetic and pharmacodynamic study of the aurora kinase inhibitor danusertib in patients with advanced or metastatic solid tumors. J Clin Oncol 2009;27:5094-101
  • Gallerani E, Delord J, Schoffski P, Phase II study of danusertib (D) in advanced/metastatic breast and ovarian cancers (BC, OC). J Clin Oncol 2010;28: 393s
  • Carpinelli P, Ceruti R, Giorgini ML, PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer. Mol Cancer Ther 2007;6:3158-68
  • Bleuse JP, Meulenbeld HJ, Vinci EM, Randomized phase II study of danusertib (D) in second-line metastatic castration-resistant prostate cancer (CRPC). J Clin Oncol 2011;29: 320s
  • Diamond JR, Bastos BR, Hansen RJ, Phase I safety, pharmacokinetic and pharmacodynamic study of ENMD-2076, a novel angiogenic and aurora kinase inhibitor, in patients with advanced solid tumors. Clin Cancer Res 2011;17:849-60
  • Phase I study of pharmacokinetics and pharmacodynamics of Aurora B/C kinase inhibitor GSK1070916A in patients with advanced solid tumors ClinicalTrialsgov 2010. Available from: http://clinicaltrials.gov/ct/show/NCT01118611 [Cited 11 November 2010]
  • Anderson K, Lai Z, McDonald OB, Biochemical characterization of GSK1070916, a potent and selective inhibitor of Aurora B and Aurora C kinases with an extremely long residence time1. Biochem J 2009;420:259-65
  • Adams ND, Adams JL, Burgess JL, Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. J Med Chem 2010;53:3973-4001
  • Minton SE, LoRusso P, Lockhart AC, A phase I study of MK-5108, an oral aurora A kinase inhibitor, in both monotherapy and in combination with docetaxel in patients with advanced solid tumors. J Clin Oncol 2010;28: 13026
  • Shimomura T, Hasako S, Nakatsuru Y, MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity alone and in combination with docetaxel. Mol Cancer Ther 2010;9:157-66
  • Phase I study evaluating MK6592 in combination with docetaxel in adult patients with relapsed or refractory advanced solid tumors. ClinicalTrialsgov 2006. Available from: http://clinicaltrials.gov/show/NCT00359671 [Cited 9 January 2011]
  • Macarulla T, Cervantes A, Elez E, Phase I study of the selective Aurora A kinase inhibitor MLN8054 in patients with advanced solid tumors: safety, pharmacokinetics, and pharmacodynamics. Mol Cancer Ther 2010;9:2844-52
  • Dees EC, Infante JR, Cohen RB, Phase 1 study of MLN8054, a selective inhibitor of Aurora A kinase in patients with advanced solid tumors. Cancer Chemother Pharmacol 2011;67:945-54
  • Manfredi MG, Ecsedy JA, Chakravarty A, Characterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays. Clin Cancer Res 2011;17:7614-24
  • Cervantes-Ruiperez A, Burris HA III, Pharmacokinetic (PK) and pharmacodynamic (PD) results from two phase I studies of the investigational selective Aurora A kinase (AAK) inhibitor MLN8237: Exposure-dependent AAK inhibition in human tumors. J Clin Oncol 2010;28: 240s
  • Cervantes-Ruiperez A, Elez ME, Rosello S, Phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of MLN8237, a novel selective aurora A kinase (AAK) inhibitor, in patients (pts) with advanced solid tumors. J Clin Oncol 2009;27: 124s
  • Dees EC, Infante JR, Burris HA, Phase I study of the investigational drug MLN8237, an Aurora A kinase (AAK) inhibitor, in patients (pts) with solid tumors. J Clin Oncol 2010. 28
  • Aurora A kinase inhibitor MLN8237 and bortezomib in treating patients with relapsed or refractory multiple myeloma. ClinicalTrialsgov 2009. Available from: http://clinicaltrials.gov/show/NCT01034553 [Cited 11 November 2010]
  • MLN8237 in adults with nonhematological malignancies, followed by MLN8237 in lung, breast, head and neck or gastroesophageal malignancies. ClinicalTrialsgov 2010. Available from: http://clinicaltrials.gov/show/NCT01045421 [Cited 11 November 2010]
  • MLN8237 in patients with ovarian, fallopian tube or peritoneal cancer preceded by Phase 1 study of MLN8237 plus paclitaxel treatment of ovary or breast cancer. ClinicalTrialsgov 2010. Available from: http://clinicaltrials.gov/show/NCT01091428 [Cited 11 November 2010]
  • Study of MLN8237 in patients with castration-resistant prostate cancer receiving a standard docetaxel/prednisone regimen. ClinicalTrialsgov 2010. Available from: http://clinicaltrials.gov/show/NCT01094288 [Cited 11 November 2010]
  • Study of MLN8237 in patients with advanced hematological malignancies ClinicalTrialsgov 2008. Available from: http://clinicaltrials.gov/show/NCT00697346 [Cited 11 November 2010]
  • Study of an oral formulation of MLN8237 in patients with advanced solid tumors. ClinicalTrialsgov 2009. Available from: http://clinicaltrials.gov/show/NCT00962091 [Cited 11 November 2010]
  • Padmanabhan S, Shea TC, Vose JM, Phase I study of an investigational Aurora A kinase inhibitor MLN8237 in patients with advanced hematologic malignancies. Blood 2010;116: 1154
  • Goldberg SL, Fenaux P, Craig MD, Phase 2 study of MLN8237, an investigational Aurora A kinase (AAK) inhibitor in patients with acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). Blood 2010;116: 341
  • Sharma S, Kurzrock R, Gouw L, Phase I dose-escalation study of the investigational Aurora A kinase (AAK) inhibitor MLN8237 as an enteric-coated tablet (ECT) formulation in patients with nonhematologic malignancies. J Clin Oncol 2011;29: 2175
  • Schoffski P, Jones SF, Dumez H, Phase I, open-label, multicentre, dose-escalation, pharmacokinetic and pharmacodynamic trial of the oral aurora kinase inhibitor PF-03814735 in advanced solid tumours. Eur J Cancer 2011;47:2256-64
  • Jani JP, Arcari J, Bernardo V, PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy. Mol Cancer Ther 2010;9:883-94
  • Robert F, Verschraegen C, Hurwitz H, A phase I trial of sns-314, a novel and selective pan-aurora kinase inhibitor, in advanced solid tumor patients. J Clin Oncol 2009;27: 117s
  • Oslob JD, Romanowski MJ, Allen DA, Discovery of a potent and selective aurora kinase inhibitor. Bioorg Med Chem Lett 2008;18:4880-4
  • Godl K, Gruss OJ, Eickhoff J, Proteomic characterization of the angiogenesis inhibitor SU6668 reveals multiple impacts on cellular kinase signaling. Cancer Res 2005;65:6919-26
  • Britten CD, Rosen LS, Kabbinavar F, Phase I trial of SU6668, a small molecule receptor tyrosine kinase inhibitor, given twice daily in patients with advanced cancers. Proceedings of the American Society of Clinical Oncology; 2002. p. 21
  • Sessa C, Vigano L, Grasselli G, Phase I clinical and pharmacological evaluation of the multi-tyrosine kinase inhibitor SU006668 by chronic oral dosing. Eur J Cancer 2006;42:171-8
  • Kuenen BC, Giaccone G, Ruijter R, Dose-finding study of the multitargeted tyrosine kinase inhibitor SU6668 in patients with advanced malignancies. Clin Cancer Res 2005;11:6240-6
  • Young MA, Shah NP, Chao LH, Structure of the kinase domain of an imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680. Cancer Res 2006;66:1007-14
  • Giles FJ, Cortes J, Jones D, MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation. Blood 2007;109:500-2
  • Giles F, Freedman SJ, Xiao A, MK-0457, a novel multikinase inhibitor, has activity in refractory AML, including transformed JAK2 positive myeloproliferative disease (MPD), and in Philadelphia-positive ALL. Blood 2006;108: 556a
  • Giles F, Bergstrom DA, Garcia-Manero G, MK-0457 is a novel Aurora kinase and Janus kinase 2 (JAK2) inhibitor with activity in transformed JAK2-positive myeloproliferative disease (MPD). Blood 2006;108: 309b
  • Rubin EH, Shapiro GI, Stein MN, A phase I clinical and pharmacokinetic (PK) trial of the aurora kinase (AK) inhibitor MK-0457 in cancer patients. J Clin Oncol 2006;24: 123s
  • Papayannidis C, Iacobucci I, Soverini S, Innovative phase I study of concomitant and consecutive treatment with dasatinib and MK-0457 in refractory Ph+ CML and ALL patients. J Clin Oncol 2009;27: 375s
  • Cortes J, Paquette R, Talpaz M, Preliminary clinical activity in a phase I trial of the BCR-ABL/IGF- 1R/Aurora kinase inhibitor XL228 in patients with Ph++ leukemias with either failure to multiple TKI therapies or with T315I mutation. Blood 2008;112:1109-10
  • Smith DC, Britten C, Garon EB, A phase I study of XL228, a multitargeted protein kinase inhibitor, in patients (pts) with solid tumors or multiple myeloma. J Clin Oncol 2010;28: 259s
  • Smith DC, Britten C, Clary DO, A phase I study of XL228, a potent IGF1R/AURORA/SRC inhibitor, in patients with solid tumors or hematologic malignancies. J Clin Oncol 2009;27: 149s
  • Ravandi F, Foran J, Verstovsek S, A phase I trial of AT9283, a multitargeted kinase inhibitor, in patients with refractory hematological malignancies. Blood 2007;110:275a-276a
  • Cortes J, Roboz GJ, Kantarjian HM, A phase I dose escalation study of KW-2449, an oral multi-kinase inhibitor against FLT3, Abl, FGFR1 and Aurora in patients with relapsed/ refractory AML, ALL and MDS or resistant/ intolerant CML. Blood 2008;112: 1019

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