{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:23:06Z","timestamp":1790166186214,"version":"4.1.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2012,7,9]],"date-time":"2012-07-09T00:00:00Z","timestamp":1341792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2012,7,9]],"date-time":"2012-07-09T00:00:00Z","timestamp":1341792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2013,1]]},"DOI":"10.1038\/leu.2012.186","type":"journal-article","created":{"date-parts":[[2012,7,9]],"date-time":"2012-07-09T06:38:08Z","timestamp":1341815888000},"page":"113-117","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["MK-0457, an Aurora kinase and BCR\u2013ABL inhibitor, is active in patients with BCR\u2013ABL T315I leukemia"],"prefix":"10.1038","volume":"27","author":[{"given":"F J","family":"Giles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R T","family":"Swords","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Nagler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Hochhaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O G","family":"Ottmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D A","family":"Rizzieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Talpaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Bergstrom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P D","family":"Le Coutre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S J","family":"Freedman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J E","family":"Cortes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,7,9]]},"reference":[{"key":"BFleu2012186_CR1","first-page":"85","volume":"16","author":"AC Burke","year":"2011","unstructured":"Burke AC, Swords RT, Kelly K, Giles FJ . Current status of agents active against the T315I chronic myeloid leukemia phenotype. Expert OpinEmerg Drugs 2011; 16: 85\u2013103.","journal-title":"Expert OpinEmerg Drugs"},{"key":"BFleu2012186_CR2","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1200\/JCO.2010.30.1820","volume":"29","author":"A Burnett","year":"2011","unstructured":"Burnett A, Wetzler M, Lowenberg B . Therapeutic advances in acute myeloid leukemia. J Clin Oncol 2011; 29: 487\u2013494.","journal-title":"J Clin Oncol"},{"key":"BFleu2012186_CR3","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/j.ceb.2009.09.008","volume":"21","author":"M Carmena","year":"2009","unstructured":"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\u2013805.","journal-title":"Curr Opin Cell Biol"},{"key":"BFleu2012186_CR4","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.cell.2007.10.002","volume":"131","author":"S Ruchaud","year":"2007","unstructured":"Ruchaud S, Carmena M, Earnshaw WC . The chromosomal passenger complex: one for all and all for one. Cell 2007; 131: 230\u2013231.","journal-title":"Cell"},{"key":"BFleu2012186_CR5","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1038\/nrm1245","volume":"4","author":"M Carmena","year":"2003","unstructured":"Carmena M, Earnshaw WC . The cellular geography of aurora kinases. Nat Rev Mol Cell Biol 2003; 4: 842\u2013854.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFleu2012186_CR6","doi-asserted-by":"publisher","first-page":"7334","DOI":"10.1074\/jbc.274.11.7334","volume":"274","author":"M Kimura","year":"1999","unstructured":"Kimura M, Matsuda Y, Yoshioka T, Okano Y . Cell cycle-dependent expression and centrosome localization of a third human aurora\/Ipl1-related protein kinase, AIK3. J Biol Chem 1999; 274: 7334\u20137340.","journal-title":"J Biol Chem"},{"key":"BFleu2012186_CR7","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1517\/17460441.2011.555395","volume":"6","author":"MR Green","year":"2011","unstructured":"Green MR, Woolery JE, Mahadevan D . Update on Aurora Kinase Targeted Therapeutics in Oncology. Expert Opin Drug Discovery 2011; 6: 291\u2013307.","journal-title":"Expert Opin Drug Discovery"},{"key":"BFleu2012186_CR8","doi-asserted-by":"publisher","first-page":"3052","DOI":"10.1093\/emboj\/17.11.3052","volume":"17","author":"JR Bischoff","year":"1998","unstructured":"Bischoff JR, Anderson L, Zhu Y, Mossie K, Ng L, Souza B et al. A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J 1998; 17: 3052\u20133065.","journal-title":"EMBO J"},{"key":"BFleu2012186_CR9","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1002\/ijc.1200","volume":"92","author":"Y Miyoshi","year":"2001","unstructured":"Miyoshi Y, Takahashi Y, Lee H, Suzuki T, Komeda T . Association of centrosomal kinase STK15\/BTAK mRNA expression with chromosomal instability in human breast cancers. Int J Cancer 2001; 92: 370\u2013373.","journal-title":"Int J Cancer"},{"key":"BFleu2012186_CR10","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1054\/bjoc.2000.1684","volume":"84","author":"C Sakakura","year":"2001","unstructured":"Sakakura C, Hagiwara A, Yasuoka R, Fujita Y, Nkanishi M, Masuda K et al. Tumour-amplified kinase BTAK is amplified and overexpressed in gastric cancers with possible involvement in aneuploid formation. Br J Cancer 2001; 84: 824\u2013831.","journal-title":"Br J Cancer"},{"key":"BFleu2012186_CR11","doi-asserted-by":"publisher","first-page":"219","DOI":"10.2174\/157489210791760517","volume":"5","author":"S Libertini","year":"2010","unstructured":"Libertini S, Abanale A, Passaro C, Botta G, Portella G, Aurora A . and B kinases-targets of novel anticancer drugs. Recent Patents Anti-Canc Dr D 2010; 5: 219\u2013241.","journal-title":"Recent Patents Anti-Canc Dr D"},{"key":"BFleu2012186_CR12","doi-asserted-by":"publisher","first-page":"482","DOI":"10.2174\/092986711794480203","volume":"18","author":"G Portella","year":"2011","unstructured":"Portella G, Passaro C, Chieffi P, Aurora B . A new prognostic marker and therapeutic target in cancer. Curr Med Chem 2011; 18: 482\u2013496.","journal-title":"Curr Med Chem"},{"key":"BFleu2012186_CR13","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/nm1003","volume":"10","author":"EA Harrington","year":"2004","unstructured":"Harrington EA, Bebbington D, Moore J, Rasmussen RK, Ajose-Adeogun AO, Nakayama T 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\u2013267.","journal-title":"Nat Med"},{"key":"BFleu2012186_CR14","first-page":"757","volume":"5","author":"D Karthigeyan","year":"2010","unstructured":"Karthigeyan D, Prasad P, Shandilya J, Agrawal S, Kundu TK . Biology of Aurora A kinase: Implications in cancer manifestation and therapy. Med Res Rev 2010; 5: 757\u2013793.","journal-title":"Med Res Rev"},{"key":"BFleu2012186_CR15","doi-asserted-by":"publisher","first-page":"2846","DOI":"10.4161\/cc.6.22.4940","volume":"6","author":"RK Tyler","year":"2007","unstructured":"Tyler RK, Shpiro N, Marquez R, Eyers PA . VX-680 inhibits Aurora A and Aurora B kinase activity in human cells. Cell Cycle 2007; 6: 2846\u20132854.","journal-title":"Cell Cycle"},{"key":"BFleu2012186_CR16","doi-asserted-by":"publisher","first-page":"3586","DOI":"10.1016\/j.bmcl.2009.04.136","volume":"19","author":"D Bebbington","year":"2009","unstructured":"Bebbington D, Binch H, Charrier JD, Everitt S, Fraysse D, Golec J et al. The discovery of the potent aurora inhibitor MK-0457 (VX-680). Bioorg Med Chem Lett 2009; 19: 3586\u20133592.","journal-title":"Bioorg Med Chem Lett"},{"key":"BFleu2012186_CR17","first-page":"296","volume":"2","author":"Y Li","year":"2010","unstructured":"Li Y, Zhang ZF, Chen J, Huang D, Ding Y, Tan MH et al. VX680\/MK-0457, a potent and selective Aurora kinase inhibitor, targets both tumor and endothelial cells in clear cell renal cell carcinoma. Am J Transl Res 2010; 2: 296\u2013308.","journal-title":"Am J Transl Res"},{"key":"BFleu2012186_CR18","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.canlet.2006.12.004","volume":"251","author":"GM Cheetham","year":"2007","unstructured":"Cheetham GM, Charlton PA, Golec JM, Pollard JR . Structural basis for potent inhibition of the Aurora kinases and a T315I multi-drug resistant mutant form of Abl kinase by VX-680. Cancer Lett 2007; 251: 323\u2013329.","journal-title":"Cancer Lett"},{"key":"BFleu2012186_CR19","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s00280-010-1318-9","volume":"67","author":"AM Traynor","year":"2011","unstructured":"Traynor AM, Hewitt M, Liu G, Flaherty KT, Clark J, Scott BB et al. Phase I dose escalation study of MK-0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors. Cancer Chemother Pharmacol 2011; 67: 305\u2013314.","journal-title":"Cancer Chemother Pharmacol"},{"key":"BFleu2012186_CR20","first-page":"247","volume":"123s","author":"EH Rubin","year":"2006","unstructured":"Rubin EH, Shapiro GI, Stein MN, Watson P, Bergstrom D, Xiao A 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; 123s: 247.","journal-title":"J Clin Oncol"},{"key":"BFleu2012186_CR21","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1182\/blood-2006-05-025049","volume":"109","author":"FJ Giles","year":"2007","unstructured":"Giles FJ, Cortes J, Jones D, Bergstrom D, Kantarjian H, Freedman SJ . 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\u2013502.","journal-title":"Blood"},{"key":"BFleu2012186_CR22","doi-asserted-by":"publisher","first-page":"5271","DOI":"10.1182\/blood-2009-04-219410","volume":"114","author":"FE Nicolini","year":"2009","unstructured":"Nicolini FE, Mauro MJ, Martinelli G, Kim DW, Soverini S, Muller MC et al. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation. Blood 2009; 114: 5271\u20135278.","journal-title":"Blood"},{"key":"BFleu2012186_CR23","doi-asserted-by":"publisher","first-page":"3912","DOI":"10.1158\/0008-5472.CAN-10-2259","volume":"71","author":"L Kretzner","year":"2011","unstructured":"Kretzner L, Scuto A, Dino PM, Kowolik CM, Wu J, Ventura P et al. Combining histone deacetylase inhibitor vorinostat with aurora kinase inhibitors enhances lymphoma cell killing with repression of c-Myc, hTERT, and microRNA levels. Cancer Res 2011; 71: 3912\u20133920.","journal-title":"Cancer Res"},{"key":"BFleu2012186_CR24","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.bbrc.2009.01.141","volume":"380","author":"S Okabe","year":"2009","unstructured":"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\u2013779.","journal-title":"Biochem Biophys Res Commun"},{"key":"BFleu2012186_CR25","doi-asserted-by":"publisher","first-page":"3219","DOI":"10.1158\/1078-0432.CCR-11-0234","volume":"17","author":"T Nguyen","year":"2011","unstructured":"Nguyen T, Dai Y, Attkisson E, Kramer L, Jordan N, Nguyen N et al. HDAC inhibitors potentiate the activity of the BCR\/ABL kinase inhibitor KW-2449 in imatinib-sensitive or -resistant BCR\/ABL+ leukemia cells in vitro and in vivo. Clin Cancer Res 2011; 17: 3219\u20133232.","journal-title":"Clin Cancer Res"},{"key":"BFleu2012186_CR26","doi-asserted-by":"publisher","first-page":"7668","DOI":"10.1158\/0008-5472.CAN-05-3353","volume":"66","author":"F Gizatullin","year":"2006","unstructured":"Gizatullin F, Yao Y, Kung V, Harding MW, Loda M, Shapiro GI . 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\u20137677.","journal-title":"Cancer Res"},{"key":"BFleu2012186_CR27","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1038\/cdd.2010.18","volume":"17","author":"CF Cheok","year":"2010","unstructured":"Cheok CF, Kua N, Kaldis P, Lane D . Combination of nutlin-3 and VX-680 selectively targets p53 mutant cells with reversible effects on cells expressing wild-type p53. Cell Death Differ 2010; 17: 1486\u20131500.","journal-title":"Cell Death Differ"},{"key":"BFleu2012186_CR28","doi-asserted-by":"publisher","first-page":"2886","DOI":"10.1182\/blood-2008-01-128611","volume":"112","author":"K Kojima","year":"2008","unstructured":"Kojima K, Konopleva M, Tsao T, Nakakuma H, Andreeff M . 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\u20132895.","journal-title":"Blood"},{"key":"BFleu2012186_CR29","doi-asserted-by":"publisher","first-page":"6030","DOI":"10.1182\/blood-2011-07-366930","volume":"118","author":"B Lowenberg","year":"2011","unstructured":"Lowenberg B, Muus P, Ossenkoppele G, Rousselot P, Cahn JY, Ifrah N et al. Phase I\/II study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia. Blood 2011; 118: 6030\u20136036.","journal-title":"Blood"},{"key":"BFleu2012186_CR30","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1016\/j.leukres.2011.04.008","volume":"35","author":"K Tsuboi","year":"2011","unstructured":"Tsuboi K, Yokozawa T, Sakura T, Watanabe T, Fujisawa S, Yamauchi T et al. A Phase I study to assess the safety, pharmacokinetics and efficacy of barasertib (AZD1152), an Aurora B kinase inhibitor, in Japanese patients with advanced acute myeloid leukemia. Leuk Res 2011; 35: 1384\u20131389.","journal-title":"Leuk Res"},{"key":"BFleu2012186_CR31","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1016\/j.bcp.2009.10.009","volume":"79","author":"NJ Donato","year":"2010","unstructured":"Donato NJ, Fang D, Sun H, Giannola D, Peterson LF, Talpaz M et al. 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\u2013697.","journal-title":"Biochem Pharmacol"},{"key":"BFleu2012186_CR32","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1158\/1535-7163.MCT-10-0069","volume":"9","author":"F Fei","year":"2010","unstructured":"Fei F, Stoddart S, Groffen J, Heisterkamp N et al. Activity of the Aurora kinase inhibitor VX-680 against Bcr\/Abl-positive acute lymphoblastic leukemias. Mol Cancer Ther 2010; 9: 1318\u20131327.","journal-title":"Mol Cancer Ther"},{"key":"BFleu2012186_CR33","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.1111\/j.1582-4934.2010.01218.x","volume":"15","author":"KR Kelly","year":"2011","unstructured":"Kelly KR, Ecsedy J, Medina E, Mahalingam D, Padmanabhan S, Nawrocki S et al. 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\u20132070.","journal-title":"J Cell Mol Med"},{"key":"BFleu2012186_CR34","doi-asserted-by":"publisher","first-page":"2067","DOI":"10.2174\/138945011798829410","volume":"12","author":"KR Kelly","year":"2011","unstructured":"Kelly KR, Ecsedy J, Mahalingam D, Nawrocki S, Padmanabhan S, Giles FJ et al. Targeting Aurora kinases in cancer treatment. Curr Drug Targets 2011; 12: 2067\u20132078.","journal-title":"Curr Drug Targets"},{"key":"BFleu2012186_CR35","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1111\/j.1365-2141.2011.08898.x","volume":"155","author":"SS Farag","year":"2011","unstructured":"Farag SS . The potential role of Aurora kinase inhibitors in haematological malignancies. Br J Haematol 2011; 155: 561\u2013579.","journal-title":"Br J Haematol"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/leu2012186.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/leu2012186","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/leu2012186.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T15:33:24Z","timestamp":1648740804000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/leu2012186"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,9]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,1]]}},"alternative-id":["BFleu2012186"],"URL":"https:\/\/doi.org\/10.1038\/leu.2012.186","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7,9]]},"assertion":[{"value":"11 June 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2012","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2012","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2012","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Employment or leadership position: Jason Clark, Patricia Watson, Alan Xiao, Baiteng Zhao, Donald Bergstrom, Steven J Freedman\u2014Merck. The remaining authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}