{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:59:16Z","timestamp":1790315956983,"version":"4.1.0"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"4","license":[{"start":{"date-parts":[[2015,1,22]],"date-time":"2015-01-22T00:00:00Z","timestamp":1421884800000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The molecular chaperone Hsp90 requires the assistance of immunophilins, co-chaperones, and partner proteins for the conformational maturation of client proteins. Hsp90 inhibition represents a promising anticancer strategy due to the dependence of numerous oncogenic signaling pathways upon Hsp90 function. Historically, small molecules have been designed to inhibit ATPase activity at the Hsp90 N-terminus; however, these molecules also induce the pro-survival heat shock response (HSR). Therefore, inhibitors that exhibit alternative mechanisms of action that do not elicit the HSR are actively sought. Small molecules that disrupt Hsp90-co-chaperone interactions can destabilize the Hsp90 complex without induction of the HSR, which leads to inhibition of cell proliferation. In this article, selective inhibition of F1F0 ATP synthase by cruentaren A was shown to disrupt the Hsp90-F1F0 ATP synthase interaction and result in client protein degradation without induction of the HSR.<\/jats:p>","DOI":"10.1021\/cb400906e","type":"journal-article","created":{"date-parts":[[2014,1,22]],"date-time":"2014-01-22T14:09:12Z","timestamp":1390399752000},"page":"976-985","source":"Crossref","is-referenced-by-count":23,"title":["Cruentaren A Binds F1F0 ATP\nSynthase To Modulate the Hsp90 Protein Folding Machinery"],"prefix":"10.1021","volume":"9","author":[{"given":"Jessica A.","family":"Hall","sequence":"first","affiliation":[{"name":"The University of Kansas , , 1251 Wescoe Hall Drive, Malott 4070 , , ,","place":["Lawrence, Kansas, United States, 66045-7562"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhaskar Reddy","family":"Kusuma","sequence":"additional","affiliation":[{"name":"The University of Kansas , , 1251 Wescoe Hall Drive, Malott 4070 , , ,","place":["Lawrence, Kansas, United States, 66045-7562"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary E. L.","family":"Brandt","sequence":"additional","affiliation":[{"name":"The University of Kansas , , 1251 Wescoe Hall Drive, Malott 4070 , , ,","place":["Lawrence, Kansas, United States, 66045-7562"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S. J.","family":"Blagg","sequence":"additional","affiliation":[{"name":"The University of Kansas , , 1251 Wescoe Hall Drive, Malott 4070 , , ,","place":["Lawrence, Kansas, United States, 66045-7562"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,1,22]]},"reference":[{"key":"2026090122382122800_cit1","doi-asserted-by":"crossref","first-page":"21455","DOI":"10.1016\/S0021-9258(20)80556-0","article-title":"The role\nof heat shock proteins in regulating the function, folding, and trafficking\nof the glucocorticoid receptor","volume":"268","author":"Pratt","year":"1993","journal-title":"J. Biol. Chem."},{"key":"2026090122382122800_cit2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0163-7258(98)00013-8","article-title":"The 90-kDa molecular\nchaperone family: Structure, function,\nand clinical applications. A comprehensive review","volume":"79","author":"Csermely","year":"1998","journal-title":"Pharmacol. Ther."},{"key":"2026090122382122800_cit3","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/nrm2918","article-title":"HSP90 at the hub of protein homeostasis:\nemerging mechanistic insights","volume":"11","author":"Taipale","year":"2010","journal-title":"Nat. Rev. Mol.\nCell Biol."},{"key":"2026090122382122800_cit4","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1158\/1078-0432.CCR-06-2966","article-title":"Targeting the molecular\nchaperone heat shock protein\n90 provides a multifaceted effect on diverse cell signaling pathways\nof cancer cells","volume":"13","author":"Xu","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"2026090122382122800_cit5","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1002\/cmdc.200600112","article-title":"Hsp90\nas a target for drug development","volume":"1","author":"Chaudhury","year":"2006","journal-title":"ChemMedChem"},{"key":"2026090122382122800_cit6","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1016\/j.jprot.2011.12.028","article-title":"The network interaction of the human\ncytosolic 90 kDa heat shock protein Hsp90: A target for cancer therapeutics","volume":"75","author":"da Silva","year":"2012","journal-title":"J. Proteomics"},{"key":"2026090122382122800_cit7","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s11912-010-0086-3","article-title":"Hsp90: A drug target?","volume":"12","author":"Holzbeierlein","year":"2010","journal-title":"Curr. Oncol. Rep."},{"key":"2026090122382122800_cit8","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.2174\/156802609789895656","article-title":"Strategies\nfor stalling malignancy: Targeting cancers addiction to Hsp90","volume":"9","author":"Prodromou","year":"2009","journal-title":"Curr. Top. Med. Chem."},{"key":"2026090122382122800_cit9","doi-asserted-by":"crossref","first-page":"18473","DOI":"10.1074\/jbc.R800007200","article-title":"The Hsp90 chaperone machinery","volume":"283","author":"Wandinger","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2026090122382122800_cit10","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/nrc1716","article-title":"Hsp90 and the chaperoning of cancer","volume":"5","author":"Whitesell","year":"2005","journal-title":"Nat. Rev. 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J."},{"key":"2026090122382122800_cit22","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s12192-010-0231-9","article-title":"Antitumor activity\nof efrapeptins, alone or in combination with 2-deoxyglucose, in breast\ncancer in vitro and in vivo","volume":"16","author":"Papathanassiu","year":"2011","journal-title":"Cell Stress Chaperones"},{"key":"2026090122382122800_cit23","doi-asserted-by":"crossref","first-page":"5036","DOI":"10.1002\/ejoc.200600421","article-title":"Isolation and structure elucidation\nof cruentarens A and b\u2500novel members of the benzolactone class\nof ATPase inhibitors from the Myxobacterium Byssovorax cruenta","volume":"2006","author":"Jundt","year":"2006","journal-title":"Eur. J. Org. Chem."},{"key":"2026090122382122800_cit24","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1016\/j.febslet.2007.06.069","article-title":"Cruentaren A, a highly\ncytotoxic benzolactone from Myxobacteria is a novel selective inhibitor\nof mitochondrial F1-ATPases","volume":"581","author":"Kunze","year":"2007","journal-title":"FEBS Lett."},{"key":"2026090122382122800_cit25","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/ja.2006.89","article-title":"Cruentaren, a new antifungal salicylate-type macrolide\nfrom Byssovorax cruenta (Myxobacteria) with inhibitory effect on mitochondrial\nATPase Activity","volume":"59","author":"Kunze","year":"2006","journal-title":"J. Antibiot."},{"key":"2026090122382122800_cit26","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-3-642-11416-8_2","article-title":"The Warburg phenomenon and other\nmetabolic alterations of cancer\ncells","volume-title":"Mitochondrial Genetics and Cancer","author":"Dakubo","year":"2010"},{"key":"2026090122382122800_cit27","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1023\/A:1022402915431","article-title":"Oxidative phosphorylation\nenzymes\nin normal and neoplastic cell growth","volume":"29","author":"Capuano","year":"1997","journal-title":"J. Bioenerg.\nBiomembr."},{"key":"2026090122382122800_cit28","doi-asserted-by":"crossref","first-page":"347","DOI":"10.2174\/138161213804143725","article-title":"The therapeutic\ntarget Hsp90 and\ncancer hallmarks","volume":"19","author":"Miyata","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"2026090122382122800_cit29","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.bmc.2010.10.029","article-title":"A systematic\nprotocol for the characterization of Hsp90\nmodulators","volume":"19","author":"Matts","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"2026090122382122800_cit30","doi-asserted-by":"crossref","first-page":"8217","DOI":"10.1021\/bi0497998","article-title":"Novobiocin\ninduces a distinct conformation of Hsp90 and alters Hsp90\u2013cochaperone\u2013client\ninteractions","volume":"43","author":"Yun","year":"2004","journal-title":"Biochemistry"},{"key":"2026090122382122800_cit31","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.2174\/156802609789895692","article-title":"Assays for identification of Hsp90\nInhibitors and biochemical\nmethods for discriminating their mechanism of action","volume":"9","author":"Matts","year":"2009","journal-title":"Curr. Top. Med. Chem."},{"key":"2026090122382122800_cit32","doi-asserted-by":"crossref","first-page":"7631","DOI":"10.1021\/bi000315r","article-title":"p50cdc37 is a nonexclusive\nHsp90 cohort which participates intimately in Hsp90-mediated folding\nof immature kinase molecules","volume":"39","author":"Hartson","year":"2000","journal-title":"Biochemistry"},{"key":"2026090122382122800_cit33","doi-asserted-by":"crossref","first-page":"13148","DOI":"10.1074\/jbc.M410838200","article-title":"Heat Shock Protein 90 stabilization\nof ErbB2 expression is disrupted by ATP depletion in myocytes","volume":"280","author":"Peng","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2026090122382122800_cit34","doi-asserted-by":"crossref","first-page":"13961","DOI":"10.1073\/pnas.1207912109","article-title":"Oligomycin frames\na common drug-binding site in the ATP synthase","volume":"109","author":"Symersky","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026090122382122800_cit35","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1042\/bj3640309","article-title":"Contribution by different\nfuels and metabolic pathways to the total ATP turnover of proliferating\nMCF-7 breast cancer cells","volume":"364","author":"Guppy","year":"2002","journal-title":"Biochem. J."},{"key":"2026090122382122800_cit36","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nrc3365","article-title":"Mitochondria\nand cancer","volume":"12","author":"Wallace","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"2026090122382122800_cit37","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1093\/jnci\/92.3.242","article-title":"Novobiocin and related\ncoumarins\nand depletion of Heat Shock Protein 90-dependent signaling proteins","volume":"92","author":"Marcu","year":"2000","journal-title":"J. Natl. Cancer Inst."},{"key":"2026090122382122800_cit38","doi-asserted-by":"crossref","first-page":"8901","DOI":"10.1021\/jo801312r","article-title":"The design, synthesis, and evaluation\nof coumarin ring derivatives of the novobiocin scaffold that exhibit\nantiproliferative activity","volume":"73","author":"Donnelly","year":"2008","journal-title":"J. Org. Chem."},{"key":"2026090122382122800_cit39","doi-asserted-by":"crossref","first-page":"6242","DOI":"10.1021\/ol302999v","article-title":"Synthesis\nof cruentaren A","volume":"14","author":"Kusuma","year":"2012","journal-title":"Org. Lett."}],"container-title":["ACS Chemical\nBiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/cb400906e","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acbcct\/article-pdf\/9\/4\/976\/7920863\/cb400906e.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acbcct\/article-pdf\/9\/4\/976\/7920863\/cb400906e.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:38:58Z","timestamp":1788316738000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acbcct\/article\/9\/4\/976\/776585\/Cruentaren-A-Binds-F1F0-ATP-Synthase-To-Modulate"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,22]]},"references-count":39,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2014,1,22]]},"published-print":{"date-parts":[[2014,4,18]]}},"URL":"https:\/\/doi.org\/10.1021\/cb400906e","relation":{},"ISSN":["1554-8929","1554-8937"],"issn-type":[{"value":"1554-8929","type":"print"},{"value":"1554-8937","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,22]]}}}