{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T02:44:05Z","timestamp":1773888245125,"version":"3.50.1"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100019018","name":"Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019018","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373718"],"award-info":[{"award-number":["82373718"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003345","name":"Chinese Academy of Meteorological Sciences","doi-asserted-by":"publisher","award":["CIFMs 2021-1-2M-028"],"award-info":[{"award-number":["CIFMs 2021-1-2M-028"]}],"id":[{"id":"10.13039\/501100003345","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.bioorg.2025.109293","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T23:58:22Z","timestamp":1764028702000},"page":"109293","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Structure-enabled discovery of carboxylate esters prodrugs as potential potent inhibitors targeting Glutaminase C"],"prefix":"10.1016","volume":"168","author":[{"given":"Hanyu","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shize","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengxia","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisha","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjie","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoguang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baolian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.bioorg.2025.109293_bb0005","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/s41568-021-00378-6","article-title":"Cancer metabolism: looking forward","volume":"21","author":"Mart\u00ednez-Reyes","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.bioorg.2025.109293_bb0010","doi-asserted-by":"crossref","DOI":"10.1186\/s13045-024-01527-8","article-title":"Metabolic reprogramming in the tumor microenvironment of liver cancer","volume":"17","author":"Lin","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"10.1016\/j.bioorg.2025.109293_bb0015","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.cmet.2011.07.014","article-title":"Metabolic Flux and the Regulation of Mammalian Cell Growth","volume":"14","author":"Locasale","year":"2011","journal-title":"Cell Metab."},{"key":"10.1016\/j.bioorg.2025.109293_bb0020","first-page":"1067","article-title":"Metabolic Codependencies in the tumor microenvironment, Cancer","volume":"11","author":"Dey","year":"2021","journal-title":"Discovery"},{"key":"10.1016\/j.bioorg.2025.109293_bb0025","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.1600200","article-title":"Fundamentals of cancer metabolism","volume":"2","author":"DeBerardinis","year":"2016","journal-title":"Sci. Adv."},{"key":"10.1016\/j.bioorg.2025.109293_bb0030","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the origin of Cancer cells","volume":"123","author":"Warburg","year":"1956","journal-title":"Science"},{"key":"10.1016\/j.bioorg.2025.109293_bb0035","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nrc.2016.131","article-title":"From Krebs to clinic: glutamine metabolism to cancer therapy","volume":"16","author":"Altman","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.bioorg.2025.109293_bb0040","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","article-title":"The emerging hallmarks of Cancer metabolism","volume":"23","author":"Pavlova","year":"2016","journal-title":"Cell Metab."},{"key":"10.1016\/j.bioorg.2025.109293_bb0045","first-page":"223","article-title":"A tale of two glutaminases: homologous enzymes with distinct roles in tumorigenesis, future","volume":"9","author":"Katt","year":"2017","journal-title":"Med. Chem."},{"key":"10.1016\/j.bioorg.2025.109293_bb0050","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1021\/acs.jmedchem.8b00327","article-title":"Recent Progress in the discovery of allosteric inhibitors of kidney-type Glutaminase","volume":"62","author":"Zimmermann","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.109293_bb0055","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12964-023-01449-x","article-title":"Glutamine addiction in tumor cell: oncogene regulation and clinical treatment","volume":"22","author":"Li","year":"2024","journal-title":"Cell Commun. Signal"},{"key":"10.1016\/j.bioorg.2025.109293_bb0060","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1146\/annurev.nu.15.070195.001025","article-title":"Regulation of glutaminase activity and glutamine metabolism","volume":"15","author":"Curthoys","year":"1995","journal-title":"Annu. Rev. Nutr."},{"key":"10.1016\/j.bioorg.2025.109293_bb0065","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1021\/acs.jmedchem.8b00961","article-title":"Overview of the development of Glutaminase inhibitors: achievements and future directions","volume":"62","author":"Xu","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.109293_bb0070","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1126\/science.abb5916","article-title":"Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders","volume":"371","author":"Johmura","year":"2021","journal-title":"Science"},{"key":"10.1016\/j.bioorg.2025.109293_bb0075","doi-asserted-by":"crossref","DOI":"10.1093\/gerona\/glae294","article-title":"Senolysis by GLS1 inhibition ameliorates kidney aging by inducing excessive mPTP opening through MFN1","volume":"80","author":"Chen","year":"2025","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"10.1016\/j.bioorg.2025.109293_bb0080","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1093\/dnares\/5.6.355","article-title":"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro","volume":"5","author":"Nagase","year":"1998","journal-title":"DNA Res."},{"key":"10.1016\/j.bioorg.2025.109293_bb0085","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1152\/physiolgenomics.1999.1.2.51","article-title":"Cloning and analysis of unique human glutaminase isoforms generated by tissue-specific alternative splicing","volume":"1","author":"Elgadi","year":"1999","journal-title":"Physiol. Genomics"},{"key":"10.1016\/j.bioorg.2025.109293_bb0090","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.canlet.2019.09.011","article-title":"Dysregulation of glutaminase and glutamine synthetase in cancer","volume":"467","author":"Mat\u00e9s","year":"2019","journal-title":"Cancer Lett."},{"key":"10.1016\/j.bioorg.2025.109293_bb0095","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/jcp.1040930308","article-title":"The inhibition by 6-diazo-5-oxo-l-norleucine of glutamine catabolism of the cultured human lymphoblast","volume":"93","author":"Willis","year":"1977","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.bioorg.2025.109293_bb0100","doi-asserted-by":"crossref","first-page":"8621","DOI":"10.1021\/acs.jmedchem.6b01069","article-title":"Discovery of 6-Diazo-5-oxo-l-norleucine (DON) prodrugs with enhanced CSF delivery in monkeys: a potential treatment for glioblastoma","volume":"59","author":"Rais","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.109293_bb0105","doi-asserted-by":"crossref","first-page":"eabq5925","DOI":"10.1126\/sciadv.abq5925","article-title":"Discovery of DRP-104, a tumor-targeted metabolic inhibitor prodrug","volume":"8","author":"Rais","year":"2022","journal-title":"Sci. Adv."},{"key":"10.1016\/j.bioorg.2025.109293_bb0110","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.108523","article-title":"Deciphering the landscape of allosteric glutaminase 1 inhibitors as anticancer agents","volume":"161","author":"Vagaggini","year":"2025","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.bioorg.2025.109293_bb0115","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.ccr.2010.08.009","article-title":"Targeting mitochondrial glutaminase activity inhibits oncogenic transformation","volume":"18","author":"Wang","year":"2010","journal-title":"Cancer Cell"},{"key":"10.1016\/j.bioorg.2025.109293_bb0120","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1080\/13543776.2023.2173573","article-title":"An updated patent review of glutaminase inhibitors (2019-2022)","volume":"33","author":"Wang","year":"2023","journal-title":"Expert Opin. Ther. Pat."},{"key":"10.1016\/j.bioorg.2025.109293_bb0125","doi-asserted-by":"crossref","first-page":"12957","DOI":"10.1021\/acs.jmedchem.0c01398","article-title":"Discovery of IPN60090, a clinical stage selective Glutaminase-1 (GLS-1) inhibitor with excellent pharmacokinetic and physicochemical properties","volume":"63","author":"Soth","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.109293_bb0130","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1042\/BJ20070039","article-title":"Novel mechanism of inhibition of rat kidney-type glutaminase by bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES)","volume":"406","author":"Robinson","year":"2007","journal-title":"Biochem. J."},{"key":"10.1016\/j.bioorg.2025.109293_bb0135","doi-asserted-by":"crossref","first-page":"6540","DOI":"10.1021\/acs.jmedchem.9b00260","article-title":"Discovery of a Thiadiazole-Pyridazine-based allosteric Glutaminase 1 inhibitor series that demonstrates Oral bioavailability and activity in tumor xenograft models","volume":"62","author":"Finlay","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.109293_bb0140","doi-asserted-by":"crossref","first-page":"4588","DOI":"10.1021\/acs.jmedchem.0c02044","article-title":"Structure-enabled discovery of novel macrocyclic inhibitors targeting Glutaminase 1 allosteric binding site","volume":"64","author":"Xu","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.109293_bb0145","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1021\/acsmedchemlett.3c00375","article-title":"Targeting the subpocket enables the discovery of Thiadiazole-Pyridazine derivatives as Glutaminase C inhibitors","volume":"14","author":"Sun","year":"2023","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2025.109293_bb0150","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1200\/JCO.2019.37.7_suppl.549","article-title":"CB-839, a glutaminase inhibitor, in combination with cabozantinib in patients with clear cell and papillary metastatic renal cell cancer (mRCC): results of a phase I study","volume":"37","author":"Meric-Bernstam","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.bioorg.2025.109293_bb0155","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1158\/1535-7163.MCT-13-0870","article-title":"Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer","volume":"13","author":"Gross","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.bioorg.2025.109293_bb0160","doi-asserted-by":"crossref","first-page":"893","DOI":"10.2174\/138955705774329528","article-title":"Advances in prodrug design","volume":"5","author":"Silva","year":"2005","journal-title":"Mini-Rev. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.109293_bb0165","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.addr.2017.06.013","article-title":"Prodrugs in medicinal chemistry and enzyme prodrug therapies","volume":"118","author":"Walther","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.bioorg.2025.109293_bb0170","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.ejmech.2016.10.061","article-title":"Prodrug approach: an overview of recent cases","volume":"127","author":"Abet","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.109293_bb0175","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1021\/acs.jmedchem.8b01198","article-title":"Novel 1,3,4-Selenadiazole-containing kidney-type Glutaminase inhibitors showed improved cellular uptake and antitumor activity","volume":"62","author":"Chen","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.109293_bb0180","doi-asserted-by":"crossref","DOI":"10.1016\/j.tet.2019.130550","article-title":"Transformation of aromatic bromides into aromatic nitriles with n-BuLi, pivalonitrile, and iodine under metal cyanide-free conditions","volume":"75","author":"Uchida","year":"2019","journal-title":"Tetrahedron"},{"key":"10.1016\/j.bioorg.2025.109293_bb0185","doi-asserted-by":"crossref","first-page":"10307","DOI":"10.1021\/acs.jmedchem.0c00726","article-title":"Discovery of N-Arylsulfonyl-Indole-2-Carboxamide derivatives as potent, selective, and orally bioavailable Fructose-1,6-Bisphosphatase inhibitors\u2014design, synthesis, in vivo glucose lowering effects, and X-ray crystal complex analysis","volume":"63","author":"Zhou","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.109293_bb0190","doi-asserted-by":"crossref","first-page":"732","DOI":"10.3389\/fchem.2020.00732","article-title":"Reactive oxygen species (ROS)-responsive nanomedicine for solving ischemia-reperfusion injury","volume":"8","author":"Chen","year":"2020","journal-title":"Front. Chem."}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206825011733?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206825011733?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T22:22:33Z","timestamp":1773872553000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206825011733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":38,"alternative-id":["S0045206825011733"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2025.109293","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Structure-enabled discovery of carboxylate esters prodrugs as potential potent inhibitors targeting Glutaminase C","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2025.109293","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"109293"}}