{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:09:18Z","timestamp":1791288558131,"version":"4.3.0"},"reference-count":51,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"am","delay-in-days":342,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2025,2]]},"DOI":"10.1016\/j.jpet.2024.100048","type":"journal-article","created":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T03:28:46Z","timestamp":1732937326000},"page":"100048","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"title":["Elesclomol rescues mitochondrial copper deficiency in disease models without triggering cuproptosis"],"prefix":"10.1016","volume":"392","author":[{"given":"Mohammad","family":"Zulkifli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8458-9785","authenticated-orcid":false,"given":"Krishna P.","family":"Maremanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana U.","family":"Okonkwo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ifrah","family":"Farid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal M.","family":"Gohil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jpet.2024.100048_bib1","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.1093\/hmg\/ddac156","article-title":"Newly identified disorder of copper metabolism caused by variants in CTR1, a high-affinity copper transporter","volume":"31","author":"Batzios","year":"2022","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.jpet.2024.100048_bib2","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1158\/1078-0432.CCR-06-0964","article-title":"Phase I clinical trial of STA-4783 in combination with paclitaxel in patients with refractory solid tumors","volume":"13","author":"Berkenblit","year":"2007","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.jpet.2024.100048_bib3","article-title":"Potential molecular and cellular mechanisms of the effects of cuproptosis-related genes in the cardiomyocytes of patients with diabetic heart failure: a bioinformatics analysis","volume":"15","author":"Chen","year":"2024","journal-title":"Front Endocrinol"},{"key":"10.1016\/j.jpet.2024.100048_bib4","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1128\/JB.00058-10","article-title":"Copper stress affects iron homeostasis by destabilizing iron-sulfur cluster formation in Bacillus subtilis","volume":"192","author":"Chillappagari","year":"2010","journal-title":"J\u00a0Bacteriol"},{"key":"10.1016\/j.jpet.2024.100048_bib5","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/448645a","article-title":"New uses for old drugs","volume":"448","author":"Chong","year":"2007","journal-title":"Nature"},{"key":"10.1016\/j.jpet.2024.100048_bib6","doi-asserted-by":"crossref","first-page":"14447","DOI":"10.1074\/jbc.M312693200","article-title":"Yeast contain a non-proteinaceous pool of copper in the mitochondrial matrix","volume":"279","author":"Cobine","year":"2004","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.jpet.2024.100048_bib7","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.bbamcr.2006.03.002","article-title":"Copper trafficking to the mitochondrion and assembly of copper metalloenzymes","volume":"1763","author":"Cobine","year":"2006","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.jpet.2024.100048_bib8","doi-asserted-by":"crossref","DOI":"10.1155\/2022\/5418376","article-title":"The molecular mechanisms of defective copper metabolism in diabetic cardiomyopathy","volume":"2022","author":"Cui","year":"2022","journal-title":"Oxid Med Cell Longev"},{"key":"10.1016\/j.jpet.2024.100048_bib9","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/cge.14289","article-title":"Fatal congenital copper transport defect caused by a homozygous likely pathogenic variant of SLC31A1","volume":"103","author":"Dame","year":"2023","journal-title":"Clin Genet"},{"key":"10.1016\/j.jpet.2024.100048_bib10","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1002\/iub.2802","article-title":"A\u00a0hub for regulation of mitochondrial metabolism: fatty acid and lipoic acid biosynthesis","volume":"76","author":"Dieckmann","year":"2024","journal-title":"IUBMB Life"},{"key":"10.1016\/j.jpet.2024.100048_bib11","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0167-6296(02)00126-1","article-title":"The price of innovation: new estimates of drug development costs","volume":"22","author":"DiMasi","year":"2003","journal-title":"J\u00a0Health Econ"},{"key":"10.1016\/j.jpet.2024.100048_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.cbpa.2021.102095","article-title":"Protein metalation in biology","volume":"66","author":"Foster","year":"2022","journal-title":"Curr Opin Chem Biol"},{"key":"10.1016\/j.jpet.2024.100048_bib13","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1007\/s00204-014-1355-y","article-title":"Copper: toxicological relevance and mechanisms","volume":"88","author":"Gaetke","year":"2014","journal-title":"Arch Toxicol"},{"key":"10.1016\/j.jpet.2024.100048_bib14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.tem.2022.11.001","article-title":"Mitochondrial copper in human genetic disorders","volume":"34","author":"Garza","year":"2023","journal-title":"Trends Endocrinol Metab"},{"key":"10.1016\/j.jpet.2024.100048_bib15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/13543784.2021.1840550","article-title":"Repurposing elesclomol, an investigational drug for the treatment of copper metabolism disorders","volume":"30","author":"Gohil","year":"2021","journal-title":"Expert Opin Investig Drugs"},{"key":"10.1016\/j.jpet.2024.100048_bib16","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1093\/hmg\/6.7.1037","article-title":"Molecular basis of the brindled mouse mutant (Mobr): a murine model of Menkes disease","volume":"6","author":"Grimes","year":"1997","journal-title":"Hum. Mol Genet"},{"key":"10.1016\/j.jpet.2024.100048_bib17","doi-asserted-by":"crossref","first-page":"7856","DOI":"10.1038\/s41598-020-64521-3","article-title":"Metallothioneins regulate ATP7A trafficking and control cell viability during copper deficiency and excess","volume":"10","author":"Gudekar","year":"2020","journal-title":"Sci Rep"},{"key":"10.1016\/j.jpet.2024.100048_bib18","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1126\/science.aaz8899","article-title":"Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice","volume":"368","author":"Guthrie","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.jpet.2024.100048_bib19","doi-asserted-by":"crossref","first-page":"15277","DOI":"10.1039\/D3DT02166A","article-title":"Copper trafficking systems in cells: insights into coordination chemistry and toxicity","volume":"52","author":"Han","year":"2023","journal-title":"Dalton Trans"},{"key":"10.1016\/j.jpet.2024.100048_bib20","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.celrep.2015.01.019","article-title":"The mitochondrial metallochaperone SCO1 is required to sustain expression of the high-affinity copper transporter CTR1 and preserve copper homeostasis","volume":"10","author":"Hlynialuk","year":"2015","journal-title":"Cell Rep"},{"key":"10.1016\/j.jpet.2024.100048_bib21","article-title":"Tubular dysfunction and ruptured ureter in a child with Menkes syndrome","volume":"2021","author":"Hui","year":"2021","journal-title":"Case Rep Pediatr"},{"key":"10.1016\/j.jpet.2024.100048_bib22","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1204926","article-title":"Verification of cuproptosis-related diagnostic model associated with immune infiltration in rheumatoid arthritis","volume":"14","author":"Jiang","year":"2023","journal-title":"Front Endocrinol"},{"key":"10.1016\/j.jpet.2024.100048_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2024.107139","article-title":"Copper homeostasis in chronic kidney disease and its crosstalk with ferroptosis","volume":"202","author":"Jiayi","year":"2024","journal-title":"Pharmacol Res"},{"key":"10.1016\/j.jpet.2024.100048_bib24","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/B978-0-444-59565-2.00045-9","article-title":"Inborn errors of copper metabolism","volume":"113","author":"Kaler","year":"2013","journal-title":"Handb Clin Neurol"},{"key":"10.1016\/j.jpet.2024.100048_bib25","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1056\/NEJMoa070613","article-title":"Neonatal diagnosis and treatment of Menkes disease","volume":"358","author":"Kaler","year":"2008","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jpet.2024.100048_bib26","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.3346\/jkms.2019.34.e4","article-title":"Urological problems in patients with Menkes disease","volume":"34","author":"Kim","year":"2018","journal-title":"J\u00a0Korean Med Sci"},{"key":"10.1016\/j.jpet.2024.100048_bib27","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1158\/1535-7163.MCT-08-0298","article-title":"Elesclomol induces cancer cell apoptosis through oxidative stress","volume":"7","author":"Kirshner","year":"2008","journal-title":"Mol Cancer Ther"},{"key":"10.1016\/j.jpet.2024.100048_bib28","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3389\/fnmol.2015.00072","article-title":"Mottled mice and non-mammalian models of Menkes disease","volume":"8","author":"Lenartowicz","year":"2015","journal-title":"Front Mol Neurosci"},{"key":"10.1016\/j.jpet.2024.100048_bib29","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/s12011-009-8533-4","article-title":"Effects of copper supplementation on the structure and content of elements in kidneys of mosaic mutant mice","volume":"136","author":"Lenartowicz","year":"2010","journal-title":"Biol Trace Elem Res"},{"key":"10.1016\/j.jpet.2024.100048_bib30","doi-asserted-by":"crossref","first-page":"3611","DOI":"10.1111\/bph.15178","article-title":"ARRIVE 2.0 and the British Journal of Pharmacology: updated guidance for 2020","volume":"177","author":"Lilley","year":"2020","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.jpet.2024.100048_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2024.107258","article-title":"Cardiovascular disease: Mitochondrial dynamics and mitophagy crosstalk mechanisms with novel programmed cell death and macrophage polarisation","volume":"206","author":"Liu","year":"2024","journal-title":"Pharmacol Res"},{"key":"10.1016\/j.jpet.2024.100048_bib32","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2022.996307","article-title":"HMGB1 is a mediator of cuproptosis-related sterile inflammation","volume":"10","author":"Liu","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"10.1016\/j.jpet.2024.100048_bib33","doi-asserted-by":"crossref","first-page":"8344","DOI":"10.1073\/pnas.0812808106","article-title":"The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity","volume":"106","author":"Macomber","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jpet.2024.100048_bib34","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adl4018","article-title":"SF3B1 mutations provide genetic vulnerability to copper ionophores in human acute myeloid leukemia","volume":"10","author":"Moison","year":"2024","journal-title":"Sci Adv"},{"key":"10.1016\/j.jpet.2024.100048_bib35","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1016\/j.freeradbiomed.2012.03.017","article-title":"The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells","volume":"52","author":"Nagai","year":"2012","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.jpet.2024.100048_bib36","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.cmet.2006.08.009","article-title":"Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function","volume":"4","author":"Nose","year":"2006","journal-title":"Cell Metab"},{"key":"10.1016\/j.jpet.2024.100048_bib37","doi-asserted-by":"crossref","first-page":"5452","DOI":"10.1200\/JCO.2008.17.1579","article-title":"Phase II, randomized, controlled, double-blinded trial of weekly elesclomol plus paclitaxel versus paclitaxel alone for stage IV metastatic melanoma","volume":"27","author":"O'Day","year":"2009","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.jpet.2024.100048_bib38","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1200\/JCO.2012.44.5585","article-title":"Final results of phase III SYMMETRY study: randomized, double-blind trial of elesclomol plus paclitaxel versus paclitaxel alone as treatment for chemotherapy-naive patients with advanced melanoma","volume":"31","author":"O'Day","year":"2013","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.jpet.2024.100048_bib39","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1038\/s41440-024-01636-4","article-title":"Copper's dual role: unravelling the link between copper homeostasis, cuproptosis, and cardiovascular diseases","volume":"47","author":"Parsanathan","year":"2024","journal-title":"Hypertens Res"},{"key":"10.1016\/j.jpet.2024.100048_bib40","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1146\/annurev.ge.27.120193.002253","article-title":"The function of heat-shock proteins in stress tolerance: degradation and reactivation of damaged proteins","volume":"27","author":"Parsell","year":"1993","journal-title":"Annu Rev Genet"},{"key":"10.1016\/j.jpet.2024.100048_bib41","article-title":"Reporting animal research: explanation and elaboration for the ARRIVE guidelines 2.0","volume":"18","author":"Percie du Sert","year":"2020","journal-title":"PLoS Biol"},{"key":"10.1016\/j.jpet.2024.100048_bib42","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2024.1344729","article-title":"Cuproptosis: potential new direction in diabetes research and treatment","volume":"15","author":"Qu","year":"2024","journal-title":"Front Endocrinol"},{"key":"10.1016\/j.jpet.2024.100048_bib43","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1146\/annurev-biochem-030409-143539","article-title":"Copper metallochaperones","volume":"79","author":"Robinson","year":"2010","journal-title":"Annu Rev Biochem"},{"key":"10.1016\/j.jpet.2024.100048_bib44","doi-asserted-by":"crossref","first-page":"8161","DOI":"10.1073\/pnas.1806296115","article-title":"Elesclomol restores mitochondrial function in genetic models of copper deficiency","volume":"115","author":"Soma","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jpet.2024.100048_bib45","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.abf0529","article-title":"Copper induces cell death by targeting lipoylated TCA cycle proteins","volume":"375","author":"Tsvetkov","year":"2022","journal-title":"Science"},{"key":"10.1016\/j.jpet.2024.100048_bib46","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41589-019-0291-9","article-title":"Mitochondrial metabolism promotes adaptation to proteotoxic stress","volume":"15","author":"Tsvetkov","year":"2019","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.jpet.2024.100048_bib47","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/ejhg.2009.187","article-title":"Menkes disease","volume":"18","author":"T\u00fcmer","year":"2010","journal-title":"Eur J Hum Genet"},{"key":"10.1016\/j.jpet.2024.100048_bib48","doi-asserted-by":"crossref","first-page":"840S","DOI":"10.1093\/ajcn\/88.3.840S","article-title":"Relevance of animal models for understanding mammalian copper homeostasis","volume":"88","author":"Vonk","year":"2008","journal-title":"Am J Clin Nutr"},{"key":"10.1016\/j.jpet.2024.100048_bib49","first-page":"2085","article-title":"Animal models of normal and disturbed iron and copper metabolism","volume":"149","author":"Wang","year":"2019","journal-title":"J\u00a0Nutr"},{"key":"10.1016\/j.jpet.2024.100048_bib50","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1093\/hmg\/ddp477","article-title":"Analysis of mouse models of cytochrome c oxidase deficiency owing to mutations in Sco2","volume":"19","author":"Yang","year":"2010","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.jpet.2024.100048_bib51","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2216722120","article-title":"FDX1-dependent and independent mechanisms of elesclomol-mediated intracellular copper delivery","volume":"120","author":"Zulkifli","year":"2023","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524301971?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524301971?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T20:56:08Z","timestamp":1742244968000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356524301971"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":51,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["S0022356524301971"],"URL":"https:\/\/doi.org\/10.1016\/j.jpet.2024.100048","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Elesclomol rescues mitochondrial copper deficiency in disease models without triggering cuproptosis","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jpet.2024.100048","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 American Society for Pharmacology and Experimental Therapeutics. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"100048"}}