{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T13:14:24Z","timestamp":1792761264092,"version":"4.5.0"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Cuproptosis is a new pattern of Cu-dependent cell death distinct from classic cell death pathways and characterized by aberrant lipoylated protein aggregation in TCA cycle, Fe-S cluster protein loss, HSP70 elevation, proteotoxic and oxidative stress aggravation. Previous studies on Cu homeostasis and Cu-induced cell death provide a great basis for the discovery of cuproptosis. It has gradually gathered enormous research interests and large progress has been achieved in revealing the metabolic pathways and key targets of cuproptosis, due to its role in mediating some genetic, neurodegenerative, cardiovascular and tumoral diseases. In terms of the key targets in cuproptosis metabolic pathways, they can be categorized into three types: oxidative stress, mitochondrial respiration, ubiquitin-proteasome system. And strategies for developing cuproptosis inducers and inhibitors involved in these targets have been continuously improved. Briefly, based on the essential cuproptosis targets and metabolic pathways, this paper classifies some relevant inducers and inhibitors including small molecule compounds, transcription factors and ncRNAs with the overview of principle, scientific and medical application, in order to provide reference for the cuproptosis study and target therapy in the future.<\/jats:p>","DOI":"10.3389\/fmolb.2024.1477971","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:10:43Z","timestamp":1732579843000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Novel insights into cuproptosis inducers and inhibitors"],"prefix":"10.3389","volume":"11","author":[{"given":"Ligang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiting","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.taap.2015.10.024","article-title":"Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc","volume":"289","author":"Adams","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.neuron.2008.06.018","article-title":"Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta","volume":"59","author":"Adlard","year":"2008","journal-title":"Neuron"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1007\/s10620-014-3495-6","article-title":"Prospective pilot study of a single daily dosage of trientine for the treatment of Wilson disease","volume":"60","author":"Ala","year":"2015","journal-title":"Dig. Dis. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"4924","DOI":"10.1021\/acs.inorgchem.0c00182","article-title":"Synthesis, characterization, and biological activity of hybrid thiosemicarbazone-alkylthiocarbamate metal complexes","volume":"59","author":"Andres","year":"2020","journal-title":"Inorg. Chem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/s40820-022-00894-6","article-title":"Connecting calcium-based nanomaterials and cancer: from diagnosis to therapy","volume":"14","author":"Bai","year":"2022","journal-title":"Nanomicro. Lett."},{"key":"B6","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.jtemb.2016.02.006","article-title":"Dietary copper and human health: current evidence and unresolved issues","volume":"35","author":"Bost","year":"2016","journal-title":"J. Trace Elem. Med. Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1001\/archneur.63.4.521","article-title":"Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease","volume":"63","author":"Brewer","year":"2006","journal-title":"Arch. Neurol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/ng1293-327","article-title":"The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene","volume":"5","author":"Bull","year":"1993","journal-title":"Nat. Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.ajhg.2011.08.011","article-title":"Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes","volume":"89","author":"Cameron","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.3390\/antiox10122006","article-title":"Antioxidants into nopal (Opuntia ficus-indica), important inhibitors of free radicals\u2019 formation","volume":"10","author":"Casta\u00f1eda-Arriaga","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1021\/acschemneuro.2c00144","article-title":"Neuroprotective activity of a novel synthetic rhodamine-based hydrazone against Cu2+-induced Alzheimer\u2019s disease in Drosophila","volume":"13","author":"Chauhan","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/ng0193-14","article-title":"Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein","volume":"3","author":"Chelly","year":"1993","journal-title":"Nat. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"7970","DOI":"10.1002\/jcp.29451","article-title":"EGCG regulates CTR1 expression through its pro-oxidative property in non-small-cell lung cancer cells","volume":"235","author":"Chen","year":"2020","journal-title":"J. Cell Physiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"10425","DOI":"10.1158\/0008-5472.CAN-06-2126","article-title":"Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity","volume":"66","author":"Chen","year":"2006","journal-title":"Cancer Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/s41392-022-01229-y","article-title":"Copper homeostasis and cuproptosis in health and disease","volume":"7","author":"Chen","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1002\/biof.2052","article-title":"SP1\/CTR1-mediated oxidative stress-induced cuproptosis in intervertebral disc degeneration","volume":"50","author":"Chen","year":"2024","journal-title":"Biofactors"},{"key":"B17","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1007\/s10555-017-9701-1","article-title":"Metal-based proteasomal deubiquitinase inhibitors as potential anticancer agents","volume":"36","author":"Chen","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"B18","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1073\/pnas.0809057106","article-title":"Increasing Cu bioavailability inhibits Abeta oligomers and tau phosphorylation","volume":"106","author":"Crouch","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B19","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/s41587-020-0707-9","article-title":"Mitochondrial copper depletion suppresses triple-negative breast cancer in mice","volume":"39","author":"Cui","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/0092-8674(94)90345-x","article-title":"Molecular characterization of a copper transport protein in S. cerevisiae: an unexpected role for copper in iron transport","volume":"76","author":"Dancis","year":"1994","journal-title":"Cell"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1016\/s0140-6736(72)91433-x","article-title":"Menkes' kinky-hair syndrome","volume":"1","author":"Danks","year":"1972","journal-title":"Lancet"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: an iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"B23","doi-asserted-by":"publisher","first-page":"109848","DOI":"10.1016\/j.celrep.2021.109848","article-title":"Lysosomal Zn2+ release triggers rapid, mitochondria-mediated, non-apoptotic cell death in metastatic melanoma","volume":"37","author":"Du","year":"2021","journal-title":"Cell Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/s41420-022-01297-7","article-title":"Recent progress in ferroptosis: inducers and inhibitors","volume":"8","author":"Du","year":"2022","journal-title":"Cell Death Discov."},{"key":"B25","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1080\/15384101.2017.1395533","article-title":"SOX9\/miR-130a\/CTR1 axis modulates DDP-resistance of cervical cancer cell","volume":"17","author":"Feng","year":"2018","journal-title":"Cell Cycle"},{"key":"B26","doi-asserted-by":"publisher","first-page":"4911","DOI":"10.1007\/s00210-023-02928-1","article-title":"PDE3B regulates KRT6B and increases the sensitivity of bladder cancer cells to copper ionophores","volume":"397","author":"Feng","year":"2024","journal-title":"Naunyn Schmiedeb. Arch. Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"415","DOI":"10.2174\/1568026615666150206152233","article-title":"Antioxidant effects of coumarins include direct radical scavenging, metal chelation and inhibition of ROS-producing enzymes","volume":"15","author":"Filipsk\u00fd","year":"2015","journal-title":"Curr. Top. Med. Chem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1007\/s13577-022-00748-8","article-title":"Circular RNA circPBX3 promotes cisplatin resistance of ovarian cancer cells via interacting with IGF2BP2 to stabilize ATP7A mRNA expression","volume":"35","author":"Fu","year":"2022","journal-title":"Hum. Cell"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e2006892","DOI":"10.1002\/adma.202006892","article-title":"Nanocatalytic theranostics with glutathione depletion and enhanced reactive oxygen species generation for efficient cancer therapy","volume":"33","author":"Fu","year":"2021","journal-title":"Adv. Mater."},{"key":"B30","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/s41568-021-00417-2","article-title":"Connecting copper and cancer: from transition metal signalling to metalloplasia","volume":"22","author":"Ge","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"B31","doi-asserted-by":"publisher","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":"B32","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1159\/000106066","article-title":"Phase II trial of copper depletion with tetrathiomolybdate as an antiangiogenesis strategy in patients with hormone-refractory prostate cancer","volume":"71","author":"Henry","year":"2006","journal-title":"Oncology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/s11060-016-2104-2","article-title":"A phase I study to repurpose disulfiram in combination with temozolomide to treat newly diagnosed glioblastoma after chemoradiotherapy","volume":"128","author":"Huang","year":"2016","journal-title":"J. Neurooncol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"13805","DOI":"10.1021\/jacs.3c14247","article-title":"Enzyme core spherical nucleic acid that enables enhanced cuproptosis and antitumor immune response through alleviating tumor hypoxia","volume":"146","author":"Huang","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.3390\/ijms24021667","article-title":"ATF3\/SPI1\/SLC31A1 signaling promotes cuproptosis induced by advanced glycosylation end products in diabetic myocardial injury","volume":"24","author":"Huo","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"19507","DOI":"10.1073\/pnas.1318431110","article-title":"Bioavailable copper modulates oxidative phosphorylation and growth of tumors","volume":"110","author":"Ishida","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B37","doi-asserted-by":"publisher","first-page":"100613","DOI":"10.1016\/j.ctarc.2022.100613","article-title":"Sensitization of cancer cells towards Cisplatin and Carboplatin by protein kinase D inhibitors through modulation of ATP7A\/B (copper transport ATPases)","volume":"32","author":"Janardhanan","year":"2022","journal-title":"Cancer Treat. Res. Commun."},{"key":"B38","doi-asserted-by":"publisher","first-page":"110173","DOI":"10.1016\/j.cbi.2022.110173","article-title":"Essential metals in health and disease","volume":"367","author":"Jomova","year":"2022","journal-title":"Chem. Biol. Interact."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1177\/153537020623100903","article-title":"Metallothionein redox cycle and function","volume":"231","author":"Kang","year":"2006","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"B40","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/s00204-020-02894-0","article-title":"Clioquinol inhibits dopamine-\u03b2-hydroxylase secretion and noradrenaline synthesis by affecting the redox status of ATOX1 and copper transport in human neuroblastoma SH-SY5Y cells","volume":"95","author":"Katsuyama","year":"2021","journal-title":"Arch. Toxicol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/j.jhep.2023.11.023","article-title":"Effects of tetrathiomolybdate on copper metabolism in healthy volunteers and in patients with Wilson disease","volume":"80","author":"Kirk","year":"2024","journal-title":"J. Hepatol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1080\/13510002.2016.1253449","article-title":"Morinda citrifolia mitigates rotenone-induced striatal neuronal loss in male Sprague-Dawley rats by preventing mitochondrial pathway of intrinsic apoptosis","volume":"22","author":"Kishore Kumar","year":"2017","journal-title":"Redox Rep."},{"key":"B43","doi-asserted-by":"publisher","first-page":"mfab041","DOI":"10.1093\/mtomcs\/mfab041","article-title":"6-Hydroxydopamine disrupts cellular copper homeostasis in human neuroblastoma SH-SY5Y cells","volume":"13","author":"Kondo","year":"2021","journal-title":"Metallomics"},{"key":"B44","doi-asserted-by":"publisher","first-page":"17102","DOI":"10.1039\/d4ra00590b","article-title":"Advances in chromone-based copper(ii) Schiff base complexes: synthesis, characterization, and versatile applications in pharmacology and biomimetic catalysis","volume":"14","author":"Kumar","year":"2024","journal-title":"RSC Adv."},{"key":"B45","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1002\/jat.2890","article-title":"Induction of apoptosis by antimycin A in differentiated PC12 cell line","volume":"34","author":"Lanju","year":"2014","journal-title":"J. Appl. Toxicol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3892\/ijmm.2023.5343","article-title":"Combination of the cuproptosis inducer disulfiram and anti-PD-L1 abolishes NSCLC resistance by ATP7B to regulate the HIF-1 signaling pathway","volume":"53","author":"Li","year":"2024","journal-title":"Int. J. Mol. Med."},{"key":"B47","doi-asserted-by":"publisher","first-page":"37280","DOI":"10.1021\/acsami.2c05944","article-title":"Nanotrains of DNA copper nanoclusters that triggered a cascade fenton-like reaction and glutathione depletion to doubly enhance chemodynamic therapy","volume":"14","author":"Li","year":"2022","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"B48","doi-asserted-by":"publisher","first-page":"21010","DOI":"10.1038\/srep21010","article-title":"\u03b2-elemene sensitizes hepatocellular carcinoma cells to oxaliplatin by preventing oxaliplatin-induced degradation of copper transporter 1","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"B49","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.ecoenv.2019.02.069","article-title":"Inhibition of Caspase-1-dependent pyroptosis attenuates copper-induced apoptosis in chicken hepatocytes","volume":"174","author":"Liao","year":"2019","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"B50","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1021\/tx0000623","article-title":"Reconstitution of apo-superoxide dismutase by nitric oxide-induced copper transfer from metallothioneins","volume":"13","author":"Liu","year":"2000","journal-title":"Chem. Res. Toxicol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1016\/j.ajpath.2013.06.026","article-title":"Role of collagen matrix in tumor angiogenesis and glioblastoma multiforme progression","volume":"183","author":"Mammoto","year":"2013","journal-title":"Am. J. Pathol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/jid.2014.461","article-title":"Omeprazole, a gastric proton pump inhibitor, inhibits melanogenesis by blocking ATP7A trafficking","volume":"135","author":"Matsui","year":"2015","journal-title":"J. Invest. Dermatol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/ng0193-20","article-title":"Isolation of a partial candidate gene for Menkes disease by positional cloning","volume":"3","author":"Mercer","year":"1993","journal-title":"Nat. Genet."},{"key":"B54","doi-asserted-by":"publisher","first-page":"eadl4018","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":"B55","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.ygyno.2018.10.001","article-title":"A phase II evaluation of elesclomol sodium and weekly paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer: an NRG oncology\/gynecologic oncology group study","volume":"151","author":"Monk","year":"2018","journal-title":"Gynecol. Oncol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1002\/ijc.10740","article-title":"The copper chelator trientine has an antiangiogenic effect against hepatocellular carcinoma, possibly through inhibition of interleukin-8 production","volume":"102","author":"Moriguchi","year":"2002","journal-title":"Int. J. Cancer"},{"key":"B57","doi-asserted-by":"publisher","first-page":"14714","DOI":"10.1038\/s41598-022-18872-8","article-title":"Effect of oral zinc regimens on human hepatic copper content: a randomized intervention study","volume":"12","author":"Munk","year":"2022","journal-title":"Sci. Rep."},{"key":"B58","doi-asserted-by":"publisher","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":"B59","doi-asserted-by":"publisher","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\u2019Day","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"B60","doi-asserted-by":"publisher","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\u2019Day","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"e202200701","DOI":"10.1002\/cmdc.202200701","article-title":"Terpyridine glycoconjugates and their metal complexes: antiproliferative activity and proteasome inhibition","volume":"18","author":"Panebianco","year":"2023","journal-title":"ChemMedChem"},{"key":"B62","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.athoracsur.2008.03.016","article-title":"A phase II trial of tetrathiomolybdate after surgery for malignant mesothelioma: final results","volume":"86","author":"Pass","year":"2008","journal-title":"Ann. Thorac. Surg."},{"key":"B63","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/ng1293-338","article-title":"Mapping, cloning and genetic characterization of the region containing the Wilson disease gene","volume":"5","author":"Petrukhin","year":"1993","journal-title":"Nat. Genet."},{"key":"B64","doi-asserted-by":"publisher","first-page":"110943","DOI":"10.1016\/j.cbi.2024.110943","article-title":"The copper transporter, SLC31A1, transcriptionally activated by ELF3, imbalances copper homeostasis to exacerbate cisplatin-induced acute kidney injury through mitochondrial dysfunction","volume":"393","author":"Qiu","year":"2024","journal-title":"Chem. Biol. Interact."},{"key":"B65","first-page":"5590","article-title":"LINC02362\/hsa-miR-18a-5p\/FDX1 axis suppresses proliferation and drives cuproptosis and oxaliplatin sensitivity of hepatocellular carcinoma","volume":"13","author":"Quan","year":"2023","journal-title":"Am. J. Cancer Res."},{"key":"B66","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.cbpa.2017.11.003","article-title":"Protein lipoylation: an evolutionarily conserved metabolic regulator of health and disease","volume":"42","author":"Rowland","year":"2018","journal-title":"Curr. Opin. Chem. Biol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1016\/S2468-1253(22)00270-9","article-title":"Trientine tetrahydrochloride versus penicillamine for maintenance therapy in Wilson disease (CHELATE): a randomised, open-label, non-inferiority, phase 3 trial","volume":"7","author":"Schilsky","year":"2022","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"325","DOI":"10.2174\/156800911794519770","article-title":"Clioquinol - a novel copper-dependent and independent proteasome inhibitor","volume":"11","author":"Schimmer","year":"2011","journal-title":"Curr. Cancer Drug Targets"},{"key":"B69","doi-asserted-by":"publisher","first-page":"11775","DOI":"10.1073\/pnas.1004250107","article-title":"Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe\/S cluster biosynthesis","volume":"107","author":"Sheftel","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B70","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.trsl.2010.08.007","article-title":"Effects of long-term zinc treatment in Japanese patients with Wilson disease: efficacy, stability, and copper metabolism","volume":"156","author":"Shimizu","year":"2010","journal-title":"Transl. Res."},{"key":"B71","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1007\/s10565-017-9390-0","article-title":"Proteasome inhibitors against amelanotic melanoma","volume":"33","author":"Sidor-Kaczmarek","year":"2017","journal-title":"Cell Biol. Toxicol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"567128","DOI":"10.1155\/2013\/567128","article-title":"Neuroprotective role of a novel copper chelator against a\u03b2 42 induced neurotoxicity","volume":"2013","author":"Singh","year":"2013","journal-title":"Int. J. Alzheimers Dis."},{"key":"B73","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/nature25016","article-title":"Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4","volume":"552","author":"Skrott","year":"2017","journal-title":"Nature"},{"key":"B74","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1038\/s41586-023-06017-4","article-title":"A druggable copper-signalling pathway that drives inflammation","volume":"617","author":"Solier","year":"2023","journal-title":"Nature"},{"key":"B75","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1124\/mol.108.046771","article-title":"Transcription factor Sp1 plays an important role in the regulation of copper homeostasis in mammalian cells","volume":"74","author":"Song","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"44035","DOI":"10.1074\/jbc.M111.274407","article-title":"Diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (CuII(atsm)) protects against peroxynitrite-induced nitrosative damage and prolongs survival in amyotrophic lateral sclerosis mouse model","volume":"286","author":"Soon","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B77","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1111\/ahg.12355","article-title":"MTF1 binds to metal-responsive element e within the ATP7B promoter and is a strong candidate in regulating the ATP7B expression","volume":"84","author":"Stalke","year":"2020","journal-title":"Ann. Hum. Genet."},{"key":"B78","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/0300-483x(94)90168-6","article-title":"Role of cytosolic copper, metallothionein and glutathione in copper toxicity in rat hepatoma tissue culture cells","volume":"92","author":"Steinebach","year":"1994","journal-title":"Toxicology"},{"key":"B79","doi-asserted-by":"publisher","first-page":"6523","DOI":"10.1038\/s41467-023-42025-8","article-title":"Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer","volume":"14","author":"Sun","year":"2023","journal-title":"Nat. Commun."},{"key":"B80","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1080\/10715760000300211","article-title":"Free radical scavenging and copper chelation: a potentially beneficial action of captopril","volume":"32","author":"Tamba","year":"2000","journal-title":"Free Radic. Res."},{"key":"B81","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/ng1293-344","article-title":"The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene","volume":"5","author":"Tanzi","year":"1993","journal-title":"Nat. Genet."},{"key":"B82","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s00775-019-01650-9","article-title":"Effective inhibition of copper-catalyzed production of hydroxyl radicals by deferiprone","volume":"24","author":"Timoshnikov","year":"2019","journal-title":"J. Biol. Inorg. Chem."},{"key":"B83","doi-asserted-by":"publisher","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":"B84","doi-asserted-by":"publisher","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":"B85","doi-asserted-by":"publisher","first-page":"506","DOI":"10.2174\/0929867324666171023161121","article-title":"Recent advances in antabuse (disulfiram): the importance of its metal-binding ability to its anticancer activity","volume":"25","author":"Viola-Rhenals","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"B86","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/ng0193-7","article-title":"Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase","volume":"3","author":"Vulpe","year":"1993","journal-title":"Nat. Genet."},{"key":"B87","doi-asserted-by":"publisher","first-page":"114830","DOI":"10.1016\/j.biopha.2023.114830","article-title":"The molecular mechanisms of cuproptosis and its relevance to cardiovascular disease","volume":"163","author":"Wang","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B88","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.3892\/mmr.2018.9079","article-title":"Hypoxia induces lactate secretion and glycolytic efflux by downregulating mitochondrial pyruvate carrier levels in human umbilical vein endothelial cells","volume":"18","author":"Wang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"B89","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1038\/nchem.2381","article-title":"Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation","volume":"7","author":"Wang","year":"2015","journal-title":"Nat. Chem."},{"key":"B90","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s13046-023-02720-2","article-title":"Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer","volume":"42","author":"Wang","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B91","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1177\/003591573402700341","article-title":"Kayser-fleischer ring in cornea in two cases of wilson\u2019s disease (progressive lenticular degeneration)","volume":"27","author":"Wilson","year":"1934","journal-title":"Proc. R. Soc. Med."},{"key":"B92","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s12943-023-01732-y","article-title":"Cuproptosis: mechanisms and links with cancers","volume":"22","author":"Xie","year":"2023","journal-title":"Mol. Cancer"},{"key":"B93","doi-asserted-by":"publisher","first-page":"173","DOI":"10.3390\/cells12010173","article-title":"Cuproptosis-related MiR-21-5p\/FDX1 Axis in clear cell renal cell carcinoma and its potential impact on tumor microenvironment","volume":"12","author":"Xie","year":"2022","journal-title":"Cells"},{"key":"B94","doi-asserted-by":"publisher","first-page":"101264","DOI":"10.1016\/j.xcrm.2023.101264","article-title":"Targeting the TCA cycle through cuproptosis confers synthetic lethality on ARID1A-deficient hepatocellular carcinoma","volume":"4","author":"Xing","year":"2023","journal-title":"Cell Rep. Med."},{"key":"B95","doi-asserted-by":"publisher","first-page":"114301","DOI":"10.1016\/j.biopha.2023.114301","article-title":"4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to promote cuproptosis in colorectal cancer","volume":"159","author":"Yang","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B96","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1002\/ctm2.19","article-title":"ATPase copper transporter A, negatively regulated by miR-148a-3p, contributes to cisplatin resistance in breast cancer cells","volume":"10","author":"Yu","year":"2020","journal-title":"Clin. Transl. Med."},{"key":"B97","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1158\/1535-7163.MCT-18-1080","article-title":"Combinatorial therapy of zinc metallochaperones with mutant p53 reactivation and diminished copper binding","volume":"18","author":"Zaman","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"B98","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/s00775-009-0594-5","article-title":"Tumor cellular proteasome inhibition and growth suppression by 8-hydroxyquinoline and clioquinol requires their capabilities to bind copper and transport copper into cells","volume":"15","author":"Zhai","year":"2010","journal-title":"J. Biol. Inorg. Chem."},{"key":"B99","doi-asserted-by":"publisher","first-page":"mfad010","DOI":"10.1093\/mtomcs\/mfad010","article-title":"Copper homeostasis and the ubiquitin proteasome system","volume":"15","author":"Zhang","year":"2023","journal-title":"Metallomics"},{"key":"B100","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.phymed.2018.04.058","article-title":"Curcumin enhances cisplatin sensitivity of human NSCLC cell lines through influencing Cu-Sp1-CTR1 regulatory loop","volume":"48","author":"Zhang","year":"2018","journal-title":"Phytomedicine"},{"key":"B101","doi-asserted-by":"publisher","first-page":"e202402397","DOI":"10.1002\/anie.202402397","article-title":"Glutathione induced in situ synthesis of Cu single-atom nanozymes with anaerobic glycolysis metabolism interference for boosting cuproptosis","volume":"63","author":"Zhang","year":"2024","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"B102","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s12964-020-00548-3","article-title":"Copper induce zebrafish retinal developmental defects via triggering stresses and apoptosis","volume":"18","author":"Zhao","year":"2020","journal-title":"Cell Commun. Signal"},{"key":"B103","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/j.scitotenv.2018.07.363","article-title":"SIRT1 downregulation mediated Manganese-induced neuronal apoptosis through activation of FOXO3a-Bim\/PUMA axis","volume":"646","author":"Zhao","year":"2019","journal-title":"Sci. Total Environ."},{"key":"B104","doi-asserted-by":"publisher","first-page":"e2216722120","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. U. S. A."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2024.1477971\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:10:48Z","timestamp":1732579848000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2024.1477971\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,26]]},"references-count":104,"alternative-id":["10.3389\/fmolb.2024.1477971"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2024.1477971","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,26]]},"article-number":"1477971"}}