{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T03:02:19Z","timestamp":1773975739161,"version":"3.50.1"},"reference-count":27,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100002865","name":"Chongqing Science and Technology Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1016\/j.ejmech.2021.113225","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T21:42:38Z","timestamp":1611783758000},"page":"113225","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"special_numbering":"C","title":["Synthesis, biological evaluation and structure-activity relationship of novel dichloroacetophenones targeting pyruvate dehydrogenase kinases with potent anticancer activity"],"prefix":"10.1016","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4857-3815","authenticated-orcid":false,"given":"Biao","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Peng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingwang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ding","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanfei","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kin Yip","family":"Tam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shao-Lin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2021.113225_bib1","doi-asserted-by":"crossref","first-page":"6893","DOI":"10.1021\/acs.chemrev.7b00775","article-title":"Cancer metabolism: current understanding and therapies","volume":"118","author":"Counihan","year":"2018","journal-title":"Chem. Rev."},{"key":"10.1016\/j.ejmech.2021.113225_bib2","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"Vander Heiden","year":"2009","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2021.113225_bib3","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg effect: how does it benefit cancer cells?","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.ejmech.2021.113225_bib4","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/j.drudis.2015.03.012","article-title":"Development of pyruvate dehydrogenase kinase inhibitors in medicinal chemistry with particular emphasis as anticancer agents","volume":"20","author":"Zhang","year":"2015","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.ejmech.2021.113225_bib5","first-page":"1407","article-title":"Targeting cancer metabolism to develop human lactate dehydrogenase (hLDH) 5 inhibitors, Drug Discov","volume":"23","author":"Zhang","year":"2018","journal-title":"Today Off."},{"key":"10.1016\/j.ejmech.2021.113225_bib6","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.7150\/ijbs.13325","article-title":"Targeting tumor metabolism for cancer treatment: is pyruvate dehydrogenase kinases (PDKs) a viable anticancer target?","volume":"11","author":"Zhang","year":"2015","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.ejmech.2021.113225_bib7","doi-asserted-by":"crossref","first-page":"22700","DOI":"10.1074\/jbc.M801765200","article-title":"Pyruvate dehydrogenase complex activity controls metabolic and malignant phenotype in cancer cells","volume":"283","author":"McFate","year":"2008","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ejmech.2021.113225_bib8","doi-asserted-by":"crossref","first-page":"28064","DOI":"10.1074\/jbc.271.45.28064","article-title":"Activated function of the pyruvate dehydrogenase phosphatase through Ca2+-facilitated binding to the inner lipoyl domain of the dihydrolipoyl acetyltransferase","volume":"271","author":"Chen","year":"1996","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ejmech.2021.113225_bib9","doi-asserted-by":"crossref","first-page":"13086","DOI":"10.1074\/jbc.M806563200","article-title":"Subunit and catalytic component stoichiometries of an in\u00a0vitro reconstituted human pyruvate dehydrogenase complex","volume":"284","author":"Brautigam","year":"2009","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ejmech.2021.113225_bib10","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3892\/ijo.2012.1687","article-title":"Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target","volume":"42","author":"Hur","year":"2013","journal-title":"Int. J. Oncol."},{"key":"10.1016\/j.ejmech.2021.113225_bib11","first-page":"1476","article-title":"Lung cancer: a comparative study of metabolism related protein expression in cancer cells and tumor associated stroma","volume":"6","author":"Koukourakis","year":"2007","journal-title":"Canc. Biol. Ther."},{"key":"10.1016\/j.ejmech.2021.113225_bib12a","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1038\/sj.bjc.6604356","article-title":"PDK-1 regulates lactate production in hypoxia and is associated with poor prognosis in head and neck squamous cancer","volume":"98","author":"Wigfield","year":"2008","journal-title":"Br. J. Canc."},{"key":"10.1016\/j.ejmech.2021.113225_bib12b","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1593\/neo.04373","article-title":"Pyruvate dehydrogenase and pyruvate dehydrogenase kinase expression in non-small cell lung cancer and tumor-associated stroma","volume":"7","author":"Koukourakis","year":"2005","journal-title":"Neoplasia"},{"key":"10.1016\/j.ejmech.2021.113225_bib13","doi-asserted-by":"crossref","first-page":"9832","DOI":"10.1021\/jm5010144","article-title":"Discovery and optimization of 4,5-diarylisoxazoles as potent dual inhibitors of pyruvate dehydrogenase kinase and heat shock protein 90","volume":"57","author":"Meng","year":"2014","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2021.113225_bib14","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1021\/acs.jmedchem.6b01478","article-title":"Application of off-rate screening in the identification of novel pan-isoform inhibitors of pyruvate dehydrogenase kinase","volume":"60","author":"Brough","year":"2017","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2021.113225_bib15","doi-asserted-by":"crossref","first-page":"4923","DOI":"10.1158\/0008-5472.CAN-15-1023","article-title":"JX06 selectively inhibits pyruvate dehydrogenase kinase PDK1 by a covalent cysteine modification","volume":"75","author":"Sun","year":"2015","journal-title":"Canc. Res."},{"key":"10.1016\/j.ejmech.2021.113225_bib16","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1021\/acs.jmedchem.6b01245","article-title":"Development of the first generation of disulfide-based subtype-selective and potent covalent pyruvate dehydrogenase kinase 1 (PDK1) inhibitors","volume":"60","author":"Liu","year":"2017","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2021.113225_bib17","doi-asserted-by":"crossref","first-page":"3562","DOI":"10.1021\/acs.jmedchem.5b01828","article-title":"Unexpected discovery of dichloroacetate derived adenosine triphosphate competitors targeting pyruvate dehydrogenase kinase to inhibit cancer proliferation","volume":"59","author":"Zhang","year":"2016","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2021.113225_bib18","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1021\/acs.jmedchem.6b01540","article-title":"Development of dihydroxyphenyl sulfonylisoindoline derivatives as liver-targeting pyruvate dehydrogenase kinase inhibitors","volume":"60","author":"Tso","year":"2017","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2021.113225_bib19","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.ejmech.2018.06.012","article-title":"Rational design of mitochondria-targeted pyruvate dehydrogenase kinase 1 inhibitors with improved selectivity and antiproliferative activity","volume":"155","author":"Xu","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2021.113225_bib20","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/ijc.25728","article-title":"Anticancer drugs that target metabolism: is dichloroacetatethe new paradigm?","volume":"128","author":"Papandreou","year":"2011","journal-title":"Int. J. Canc."},{"key":"10.1016\/j.ejmech.2021.113225_bib21","doi-asserted-by":"crossref","first-page":"31ra34","DOI":"10.1126\/scitranslmed.3000677","article-title":"Metabolic modulation of glioblastoma with dichloroacetate","volume":"2","author":"Michelakis","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ejmech.2021.113225_bib22","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1016\/j.addr.2008.02.014","article-title":"Role of dichloroacetate in the treatment of genetic mitochondrial diseases","volume":"60","author":"Stacpoole","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejmech.2021.113225_bib23","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1002\/ddr.430350303","article-title":"Inhibition of pyruvate dehydrogenase kinase by halogenated acetophenones","volume":"35","author":"Espinal","year":"1995","journal-title":"Drug Dev. Res."},{"key":"10.1016\/j.ejmech.2021.113225_bib24","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ejps.2018.07.026","article-title":"Anticancer effects of some novel dichloroacetophenones through the inhibition of pyruvate dehydrogenase kinase","volume":"123","author":"Zhang","year":"2018","journal-title":"Eur. J. Pharmaceut. Sci."},{"key":"10.1016\/j.ejmech.2021.113225_bib25","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1016\/j.bmcl.2018.09.026","article-title":"Dichloroacetophenones targeting at pyruvate dehydrogenase kinase 1 with improved selectivity and antiproliferative activity: synthesis and structure activity relationships","volume":"28","author":"Zhang","year":"2018","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2021.113225_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112579","article-title":"Development of dual inhibitors targeting pyruvate dehydrogenase kinases and human lactate dehydrogenase A: high-throughput virtual screening, synthesis and biological validation","volume":"203","author":"Xiang","year":"2020","journal-title":"Eur. J. Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352342100074X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352342100074X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:20:10Z","timestamp":1759328410000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S022352342100074X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":27,"alternative-id":["S022352342100074X"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2021.113225","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Synthesis, biological evaluation and structure-activity relationship of novel dichloroacetophenones targeting pyruvate dehydrogenase kinases with potent anticancer activity","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2021.113225","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"113225"}}