{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T19:16:55Z","timestamp":1761765415995},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2011,5,12]],"date-time":"2011-05-12T00:00:00Z","timestamp":1305158400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"DOI":"10.1038\/cddis.2011.39","type":"journal-article","created":{"date-parts":[[2011,5,12]],"date-time":"2011-05-12T10:11:14Z","timestamp":1305195074000},"page":"e156-e156","update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Blockade of Hsp90 by 17AAG antagonizes MDMX and synergizes with Nutlin to induce p53-mediated apoptosis in solid tumors"],"prefix":"10.1038","volume":"2","author":[{"given":"A V","family":"Vaseva","sequence":"first","affiliation":[]},{"given":"A R","family":"Yallowitz","sequence":"additional","affiliation":[]},{"given":"N D","family":"Marchenko","sequence":"additional","affiliation":[]},{"given":"S","family":"Xu","sequence":"additional","affiliation":[]},{"given":"U M","family":"Moll","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2011,5,12]]},"reference":[{"key":"BFcddis201139_CR1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/cgt.2010.63","volume":"18","author":"I Goldstein","year":"2011","unstructured":"Goldstein I, Marcel V, Olivier M, Oren M, Rotter V, Hainaut P . Understanding wild-type and mutant p53 activities in human cancer: new landmarks on the way to targeted therapies. Cancer Gene Ther 2011; 18: 2\u201311.","journal-title":"Cancer Gene Ther"},{"key":"BFcddis201139_CR2","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1016\/j.cell.2006.12.007","volume":"127","author":"CP Martins","year":"2006","unstructured":"Martins CP, Brown-Swigart L, Evan GI . Modeling the therapeutic efficacy of p53 restoration in tumors. Cell 2006; 127: 1323\u20131334.","journal-title":"Cell"},{"key":"BFcddis201139_CR3","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nature05541","volume":"445","author":"A Ventura","year":"2007","unstructured":"Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L et al. Restoration of p53 function leads to tumour regression in vivo. Nature 2007; 445: 661\u2013665.","journal-title":"Nature"},{"key":"BFcddis201139_CR4","doi-asserted-by":"publisher","first-page":"1918","DOI":"10.1158\/0008-5472.CAN-04-3576","volume":"65","author":"D Carvajal","year":"2005","unstructured":"Carvajal D, Tovar C, Yang H, Vu BT, Heimbrook DC, Vassilev LT . Activation of p53 by MDM2 antagonists can protect proliferating cells from mitotic inhibitors. Cancer Res 2005; 65: 1918\u20131924.","journal-title":"Cancer Res"},{"key":"BFcddis201139_CR5","doi-asserted-by":"publisher","first-page":"419","DOI":"10.4161\/cc.3.4.801","volume":"3","author":"LT Vassilev","year":"2004","unstructured":"Vassilev LT . Small-molecule antagonists of p53\u2013MDM2 binding: research tools and potential therapeutics. Cell Cycle 2004; 3: 419\u2013421.","journal-title":"Cell Cycle"},{"key":"BFcddis201139_CR6","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1126\/science.1092472","volume":"303","author":"LT Vassilev","year":"2004","unstructured":"Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004; 303: 844\u2013848.","journal-title":"Science"},{"key":"BFcddis201139_CR7","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1136\/jcp.2009.070961","volume":"63","author":"MN Saha","year":"2010","unstructured":"Saha MN, Micallef J, Qiu L, Chang H . Pharmacological activation of the p53 pathway in haematological malignancies. J Clin Pathol 2010; 63: 204\u2013209.","journal-title":"J Clin Pathol"},{"key":"BFcddis201139_CR8","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.molmed.2006.11.002","volume":"13","author":"LT Vassilev","year":"2007","unstructured":"Vassilev LT . MDM2 inhibitors for cancer therapy. Trends Mol Med 2007; 13: 23\u201331.","journal-title":"Trends Mol Med"},{"key":"BFcddis201139_CR9","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1073\/pnas.0507493103","volume":"103","author":"C Tovar","year":"2006","unstructured":"Tovar C, Rosinski J, Filipovic Z, Higgins B, Kolinsky K, Hilton H et al. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci USA 2006; 103: 1888\u20131893.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis201139_CR10","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1158\/1541-7786.MCR-09-0144","volume":"7","author":"B Huang","year":"2009","unstructured":"Huang B, Deo D, Xia M, Vassilev LT . Pharmacologic p53 activation blocks cell cycle progression but fails to induce senescence in epithelial cancer cells. Mol Cancer Res 2009; 7: 1497\u20131509.","journal-title":"Mol Cancer Res"},{"key":"BFcddis201139_CR11","doi-asserted-by":"publisher","first-page":"9660","DOI":"10.1073\/pnas.1002298107","volume":"107","author":"ZN Demidenko","year":"2010","unstructured":"Demidenko ZN, Korotchkina LG, Gudkov AV, Blagosklonny MV . Paradoxical suppression of cellular senescence by p53. Proc Natl Acad Sci USA 2010; 107: 9660\u20139664.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis201139_CR12","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/onc.2010.413","volume":"30","author":"M Xia","year":"2011","unstructured":"Xia M, Knezevic D, Vassilev LT . p21 does not protect cancer cells from apoptosis induced by nongenotoxic p53 activation. Oncogene 2011; 30: 346\u2013355.","journal-title":"Oncogene"},{"key":"BFcddis201139_CR13","doi-asserted-by":"publisher","first-page":"33036","DOI":"10.1074\/jbc.M605405200","volume":"281","author":"M Wade","year":"2006","unstructured":"Wade M, Wong ET, Tang M, Stommel JM, Wahl GM . Hdmx modulates the outcome of p53 activation in human tumor cells. J Biol Chem 2006; 281: 33036\u201333044.","journal-title":"J Biol Chem"},{"key":"BFcddis201139_CR14","doi-asserted-by":"publisher","first-page":"33030","DOI":"10.1074\/jbc.C600147200","volume":"281","author":"B Hu","year":"2006","unstructured":"Hu B, Gilkes DM, Farooqi B, Sebti SM, Chen J . MDMX overexpression prevents p53 activation by the MDM2 inhibitor Nutlin. J Biol Chem 2006; 281: 33030\u201333035.","journal-title":"J Biol Chem"},{"key":"BFcddis201139_CR15","doi-asserted-by":"publisher","first-page":"3169","DOI":"10.1158\/0008-5472.CAN-05-3832","volume":"66","author":"JT Patton","year":"2006","unstructured":"Patton JT, Mayo LD, Singhi AD, Gudkov AV, Stark GR, Jackson MW . Levels of HdmX expression dictate the sensitivity of normal and transformed cells to Nutlin-3. Cancer Res 2006; 66: 3169\u20133176.","journal-title":"Cancer Res"},{"key":"BFcddis201139_CR16","doi-asserted-by":"publisher","first-page":"689","DOI":"10.2174\/156800907782418266","volume":"7","author":"NA Laurie","year":"2007","unstructured":"Laurie NA, Shih CS, Dyer MA . Targeting MDM2 and MDMX in retinoblastoma. Curr Cancer Drug Targets 2007; 7: 689\u2013695.","journal-title":"Curr Cancer Drug Targets"},{"key":"BFcddis201139_CR17","doi-asserted-by":"publisher","first-page":"8810","DOI":"10.1158\/0008-5472.CAN-07-1140","volume":"67","author":"B Hu","year":"2007","unstructured":"Hu B, Gilkes DM, Chen J . Efficient p53 activation and apoptosis by simultaneous disruption of binding to MDM2 and MDMX. Cancer Res 2007; 67: 8810\u20138817.","journal-title":"Cancer Res"},{"key":"BFcddis201139_CR18","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/nrc1716","volume":"5","author":"L Whitesell","year":"2005","unstructured":"Whitesell L, Lindquist SL . HSP90 and the chaperoning of cancer. Nat Rev Cancer 2005; 5: 761\u2013772.","journal-title":"Nat Rev Cancer"},{"key":"BFcddis201139_CR19","doi-asserted-by":"publisher","first-page":"8379","DOI":"10.1073\/pnas.93.16.8379","volume":"93","author":"MV Blagosklonny","year":"1996","unstructured":"Blagosklonny MV, Toretsky J, Bohen S, Neckers L . Mutant conformation of p53 translated in vitro or in vivo requires functional HSP90. Proc Natl Acad Sci USA 1996; 93: 8379\u20138383.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis201139_CR20","doi-asserted-by":"publisher","first-page":"40583","DOI":"10.1074\/jbc.M102817200","volume":"276","author":"Y Peng","year":"2001","unstructured":"Peng Y, Chen L, Li C, Lu W, Chen J . Inhibition of MDM2 by hsp90 contributes to mutant p53 stabilization. J Biol Chem 2001; 276: 40583\u201340590.","journal-title":"J Biol Chem"},{"key":"BFcddis201139_CR21","doi-asserted-by":"publisher","first-page":"48836","DOI":"10.1074\/jbc.M407601200","volume":"279","author":"D Walerych","year":"2004","unstructured":"Walerych D, Kudla G, Gutkowska M, Wawrzynow B, Muller L, King FW et al. Hsp90 chaperones wild-type p53 tumor suppressor protein. J Biol Chem 2004; 279: 48836\u201348845.","journal-title":"J Biol Chem"},{"key":"BFcddis201139_CR22","doi-asserted-by":"publisher","first-page":"48846","DOI":"10.1074\/jbc.M407687200","volume":"279","author":"L Muller","year":"2004","unstructured":"Muller L, Schaupp A, Walerych D, Wegele H, Buchner J . Hsp90 regulates the activity of wild type p53 under physiological and elevated temperatures. J Biol Chem 2004; 279: 48846\u201348854.","journal-title":"J Biol Chem"},{"key":"BFcddis201139_CR23","doi-asserted-by":"publisher","first-page":"14626","DOI":"10.1074\/jbc.M610514200","volume":"282","author":"M Sasaki","year":"2007","unstructured":"Sasaki M, Nie L, Maki CG . MDM2 binding induces a conformational change in p53 that is opposed by heat-shock protein 90 and precedes p53 proteasomal degradation. J Biol Chem 2007; 282: 14626\u201314634.","journal-title":"J Biol Chem"},{"key":"BFcddis201139_CR24","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1038\/sj.onc.1210893","volume":"27","author":"K Lin","year":"2008","unstructured":"Lin K, Rockliffe N, Johnson GG, Sherrington PD, Pettitt AR . Hsp90 inhibition has opposing effects on wild-type and mutant p53 and induces p21 expression and cytotoxicity irrespective of p53\/ATM status in chronic lymphocytic leukaemia cells. Oncogene 2008; 27: 2445\u20132455.","journal-title":"Oncogene"},{"key":"BFcddis201139_CR25","doi-asserted-by":"publisher","first-page":"17037","DOI":"10.1073\/pnas.0902880106","volume":"106","author":"O Ayrault","year":"2009","unstructured":"Ayrault O, Godeny MD, Dillon C, Zindy F, Fitzgerald P, Roussel MF et al. Inhibition of Hsp90 via 17-DMAG induces apoptosis in a p53-dependent manner to prevent medulloblastoma. Proc Natl Acad Sci USA 2009; 106: 17037\u201317042.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis201139_CR26","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.tcb.2010.01.009","volume":"20","author":"M Wade","year":"2010","unstructured":"Wade M, Wang YV, Wahl GM . The p53 orchestra: Mdm2 and Mdmx set the tone. Trends Cell Biol 2010; 20: 299\u2013309.","journal-title":"Trends Cell Biol"},{"key":"BFcddis201139_CR27","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","volume":"70","author":"TC Chou","year":"2010","unstructured":"Chou TC . Drug combination studies and their synergy quantification using the Chou\u2013Talalay method. Cancer Res 2010; 70: 440\u2013446.","journal-title":"Cancer Res"},{"key":"BFcddis201139_CR28","doi-asserted-by":"publisher","first-page":"2438","DOI":"10.1101\/gad.10.19.2438","volume":"10","author":"X Chen","year":"1996","unstructured":"Chen X, Ko LJ, Jayaraman L, Prives C . p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev 1996; 10: 2438\u20132451.","journal-title":"Genes Dev"},{"key":"BFcddis201139_CR29","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.4161\/cc.8.11.8596","volume":"8","author":"AV Vaseva","year":"2009","unstructured":"Vaseva AV, Marchenko ND, Moll UM . The transcription-independent mitochondrial p53 program is a major contributor to nutlin-induced apoptosis in tumor cells. Cell Cycle 2009; 8: 1711\u20131719.","journal-title":"Cell Cycle"},{"key":"BFcddis201139_CR30","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/nature05194","volume":"444","author":"NA Laurie","year":"2006","unstructured":"Laurie NA, Donovan SL, Shih CS, Zhang J, Mills N, Fuller C et al. Inactivation of the p53 pathway in retinoblastoma. Nature 2006; 444: 61\u201366.","journal-title":"Nature"},{"key":"BFcddis201139_CR31","first-page":"277","volume":"4","author":"A Kamal","year":"2004","unstructured":"Kamal A, Burrows FJ . Hsp90 inhibitors as selective anticancer drugs. Discov Med 2004; 4: 277\u2013280.","journal-title":"Discov Med"},{"key":"BFcddis201139_CR32","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1158\/1535-7163.MCT-08-0179","volume":"7","author":"N Zhu","year":"2008","unstructured":"Zhu N, Gu L, Li F, Zhou M . Inhibition of the Akt\/survivin pathway synergizes the antileukemia effect of nutlin-3 in acute lymphoblastic leukemia cells. Mol Cancer Ther 2008; 7: 1101\u20131109.","journal-title":"Mol Cancer Ther"},{"key":"BFcddis201139_CR33","first-page":"440","volume":"70","author":"G Zauli","year":"2010","unstructured":"Zauli G, Voltan R, Bosco R, Melloni E, Marmiroli S, Rigolin GM et al. Dasatinib plus Nutlin-3 shows synergistic anti-leukemic activity in both p53wild-type and p53mutated B chronic lymphocytic leukemias by inhibiting the Akt pathway. Clin Cancer Res 2010; 70: 440\u2013446.","journal-title":"Clin Cancer Res"},{"key":"BFcddis201139_CR34","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.4161\/cc.9.6.10956","volume":"9","author":"GM Popowicz","year":"2010","unstructured":"Popowicz GM, Czarna A, Wolf S, Wang K, Wang W, Domling A et al. Structures of low molecular weight inhibitors bound to MDMX and MDM2 reveal new approaches for p53\u2013MDMX\/MDM2 antagonist drug discovery. Cell Cycle 2010; 9: 1104\u20131111.","journal-title":"Cell Cycle"},{"key":"BFcddis201139_CR35","doi-asserted-by":"publisher","first-page":"10786","DOI":"10.1074\/jbc.M109.056747","volume":"285","author":"D Reed","year":"2010","unstructured":"Reed D, Shen Y, Shelat AA, Arnold LA, Ferreira AM, Zhu F et al. Identification and characterization of the first small molecule inhibitor of MDMX. J Biol Chem 2010; 285: 10786\u201310796.","journal-title":"J Biol Chem"},{"key":"BFcddis201139_CR36","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1158\/1535-7163.MCT-10-0581","volume":"10","author":"H Wang","year":"2011","unstructured":"Wang H, Ma X, Ren S, Buolamwini JK, Yan C . A small-molecule inhibitor of MDMX activates p53 and induces apoptosis. Mol Cancer Ther 2011; 10: 69\u201379.","journal-title":"Mol Cancer Ther"},{"key":"BFcddis201139_CR37","doi-asserted-by":"publisher","first-page":"2424","DOI":"10.1158\/0008-5472.CAN-09-0878","volume":"70","author":"W Zhang","year":"2010","unstructured":"Zhang W, Konopleva M, Burks JK, Dywer KC, Schober WD, Yang JY et al. Blockade of mitogen-activated protein kinase\/extracellular signal-regulated kinase kinase and murine double minute synergistically induces apoptosis in acute myeloid leukemia via BH3-only proteins Puma and Bim. Cancer Res 2010; 70: 2424\u20132434.","journal-title":"Cancer Res"},{"key":"BFcddis201139_CR38","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/S1535-6108(03)00029-1","volume":"3","author":"JS Isaacs","year":"2003","unstructured":"Isaacs JS, Xu W, Neckers L . Heat shock protein 90 as a molecular target for cancer therapeutics. Cancer Cell 2003; 3: 213\u2013217.","journal-title":"Cancer Cell"},{"key":"BFcddis201139_CR39","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/nature01913","volume":"425","author":"A Kamal","year":"2003","unstructured":"Kamal A, Thao L, Sensintaffar J, Zhang L, Boehm MF, Fritz LC et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 2003; 425: 407\u2013410.","journal-title":"Nature"}],"container-title":["Cell Death & Disease"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/cddis201139.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/cddis201139","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis201139.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T23:46:57Z","timestamp":1672962417000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cddis201139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5,12]]},"references-count":39,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2011,5]]}},"alternative-id":["BFcddis201139"],"URL":"https:\/\/doi.org\/10.1038\/cddis.2011.39","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5,12]]},"assertion":[{"value":"10 March 2011","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2011","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2011","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}