{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:52:45Z","timestamp":1790085165819,"version":"4.0.1"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21521003"],"award-info":[{"award-number":["21521003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22077009"],"award-info":[{"award-number":["22077009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81400826"],"award-info":[{"award-number":["81400826"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20170412150827191"],"award-info":[{"award-number":["JCYJ20170412150827191"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20200109120408264"],"award-info":[{"award-number":["JCYJ20200109120408264"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20170818090609800"],"award-info":[{"award-number":["JCYJ20170818090609800"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017607","name":"Shenzhen Fundamental Research Program","doi-asserted-by":"publisher","award":["GXWD20201231165807007-20200811141635001"],"award-info":[{"award-number":["GXWD20201231165807007-20200811141635001"]}],"id":[{"id":"10.13039\/501100017607","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017607","name":"Shenzhen Fundamental Research Program","doi-asserted-by":"publisher","award":["GXWD20201231165807007-20200811151825001"],"award-info":[{"award-number":["GXWD20201231165807007-20200811151825001"]}],"id":[{"id":"10.13039\/501100017607","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2022,3,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Metformin and other biguanides represent a new class of inhibitors of mitochondrial complex I that show promising antitumor effects. However, stronger inhibition of mitochondrial complex I is generally associated with upregulation of glycolysis and higher risk of lactic acidosis. Herein we report a novel biguanide derivative,\n                    <jats:italic>N<\/jats:italic>\n                    \u2010cystaminylbiguanide (MC001), which was found to inhibit mitochondrial complex I with higher potency while inducing lactate production to a similar degree as metformin.Furthermore, MC001 was found to efficiently inhibit a panel of colorectal cancer (CRC) cells in\u2005vitro and to suppress tumor growth in a HCT116 xenograft nude mouse model, while not enhancing lactate production relative to metformin, exhibiting a superior safety profile to other potent biguanides such as phenformin. Mechanistically, MC001 efficiently inhibits mitochondrial complex I, activates AMPK, and represses mTOR, leading to cell\u2010cycle arrest and apoptosis. Notably, MC001 inhibits both oxidative phosphorylation (OXPHOS) and glycolysis. We therefore propose that MC001 warrants further investigation in cancer treatment.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202100674","type":"journal-article","created":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T22:23:49Z","timestamp":1641335029000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Biguanide MC001, a Dual Inhibitor of OXPHOS and Glycolysis, Shows Enhanced Antitumor Activity Without Increasing Lactate Production"],"prefix":"10.1002","volume":"17","author":[{"given":"Jiamiao","family":"Fu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Chemical Oncogenomics Key Laboratory of Chemical Genomics Peking University Shenzhen Graduate School  Shenzhen 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemical Oncogenomics Key Laboratory of Chemical Genomics Peking University Shenzhen Graduate School  Shenzhen 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minqiang","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemical Oncogenomics Key Laboratory of Chemical Genomics Peking University Shenzhen Graduate School  Shenzhen 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximing","family":"Liao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemical Oncogenomics Key Laboratory of Chemical Genomics Peking University Shenzhen Graduate School  Shenzhen 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoquan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemical Oncogenomics Key Laboratory of Chemical Genomics Peking University Shenzhen Graduate School  Shenzhen 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengshuang","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemical Oncogenomics Key Laboratory of Chemical Genomics Peking University Shenzhen Graduate School  Shenzhen 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinkai","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemical Oncogenomics Key Laboratory of Chemical Genomics Peking University Shenzhen Graduate School  Shenzhen 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1601-6130","authenticated-orcid":false,"given":"Junmin","family":"Quan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemical Oncogenomics Key Laboratory of Chemical Genomics Peking University Shenzhen Graduate School  Shenzhen 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,18]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-015-0221-y"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2017.00118"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.09.006"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2020.100143"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.02242"},{"issue":"7503","key":"e_1_2_8_6_1","first-page":"1304","volume":"330","author":"Evans J. M.","year":"2005","journal-title":"BMJ Glob. Health"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.29.02.06.dc05-1558"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-2175"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2013.256"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200219666180416161846"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.05.023"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-38007-5_21"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-10-0186"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00565-3"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.01.003"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.03.010"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2012.56"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-14-0121"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2008.08.013"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-87-5-591"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00052"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-12-0007"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.201800073"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-15-1021"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/0885066618793385"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1409844111"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3109\/14756360903179443"},{"key":"e_1_2_8_28_1","unstructured":"\u00a0"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0177"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25166"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0052-4"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3629"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.12.009"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202100674","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202100674","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202100674","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:48:28Z","timestamp":1760298508000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202100674"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,18]]},"references-count":33,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,3,18]]}},"alternative-id":["10.1002\/cmdc.202100674"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202100674","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,18]]},"assertion":[{"value":"2021-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202100674"}}