{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:53:58Z","timestamp":1792068838525,"version":"4.4.0"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004000","name":"Guangzhou Municipal Science and Technology Program key projects","doi-asserted-by":"publisher","award":["2025A04J3241"],"award-info":[{"award-number":["2025A04J3241"]}],"id":[{"id":"10.13039\/501100004000","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M751137"],"award-info":[{"award-number":["2024M751137"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404418"],"award-info":[{"award-number":["82404418"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic & Medicinal Chemistry Letters"],"published-print":{"date-parts":[[2027,1]]},"DOI":"10.1016\/j.bmcl.2026.130777","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:38:53Z","timestamp":1789054733000},"page":"130777","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Discovery of novel dual STAT3\/TrxR1 inhibitors via pharmacophore fusion as potent lead compounds for colorectal cancer"],"prefix":"10.1016","volume":"142","author":[{"given":"Yigui","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhua","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanzhu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linchong","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinghua","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmcl.2026.130777_bb0005","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1038\/521S1a","article-title":"Colorectal cancer","volume":"521","author":"Brody","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.bmcl.2026.130777_bb0010","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J Clin"},{"key":"10.1016\/j.bmcl.2026.130777_bb0015","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0301027","article-title":"Colorectal cancer survival disparities in the five regions of Georgia","volume":"19","author":"Tsai","year":"2024","journal-title":"PLoS One"},{"key":"10.1016\/j.bmcl.2026.130777_bb0020","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.tips.2023.01.003","article-title":"Metastatic colorectal cancer: mechanisms and emerging therapeutics","volume":"44","author":"Shin","year":"2023","journal-title":"Trends Pharmacol Sci"},{"key":"10.1016\/j.bmcl.2026.130777_bb0025","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1126\/science.277.5332.1630","article-title":"STATs and gene regulation","volume":"277","author":"Darnell","year":"1997","journal-title":"Science"},{"key":"10.1016\/j.bmcl.2026.130777_bb0030","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13045-024-01654-2","article-title":"Helicobacter pylori and gastric cancer: mechanisms and new perspectives","volume":"18","author":"Duan","year":"2025","journal-title":"J Hematol Oncol"},{"key":"10.1016\/j.bmcl.2026.130777_bb0035","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-021-00791-1","article-title":"The JAK\/STAT signaling pathway: from bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.bmcl.2026.130777_bb0040","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41392-023-01468-7","article-title":"Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer","volume":"8","author":"Xue","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.bmcl.2026.130777_bb0045","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/s41586-025-09000-3","article-title":"STAT5 and STAT3 balance shapes dendritic cell function and tumour immunity","volume":"643","author":"Zhou","year":"2025","journal-title":"Nature"},{"key":"10.1016\/j.bmcl.2026.130777_bb0050","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nrc1275","article-title":"The STATs of cancer--new molecular targets come of age","volume":"4","author":"Yu","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.bmcl.2026.130777_bb0055","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/nrc2734","article-title":"STATs in cancer inflammation and immunity: a leading role for STAT3","volume":"9","author":"Yu","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.bmcl.2026.130777_bb0060","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1158\/1078-0432.CCR-10-2694","article-title":"STAT3 expression, molecular features, inflammation patterns, and prognosis in a database of 724 colorectal cancers","volume":"17","author":"Morikawa","year":"2011","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.bmcl.2026.130777_bb0065","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1002\/med.21886","article-title":"Targeting key proteins involved in transcriptional regulation for cancer therapy: current strategies and future prospective","volume":"42","author":"Pei","year":"2022","journal-title":"Med Res Rev"},{"key":"10.1016\/j.bmcl.2026.130777_bb0070","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1126\/science.278.5344.1803","article-title":"Specific inhibition of Stat3 signal transduction by PIAS3","volume":"278","author":"Chung","year":"1997","journal-title":"Science"},{"key":"10.1016\/j.bmcl.2026.130777_bb0075","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.smim.2013.12.004","article-title":"Inhibition of IL-6 family cytokines by SOCS3","volume":"26","author":"Babon","year":"2014","journal-title":"Semin Immunol"},{"key":"10.1016\/j.bmcl.2026.130777_bb0080","doi-asserted-by":"crossref","first-page":"6645","DOI":"10.1021\/jm300207s","article-title":"Small molecule inhibitors of signal transducer and activator of transcription 3 (Stat3) protein","volume":"55","author":"Debnath","year":"2012","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2026.130777_bb0085","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1002\/med.21574","article-title":"JNK signaling in cancer cell survival","volume":"39","author":"Wu","year":"2019","journal-title":"Med Res Rev"},{"key":"10.1016\/j.bmcl.2026.130777_bb0090","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1016\/j.bmc.2010.12.010","article-title":"Design, synthesis, and in vitro characterization of novel hybrid peptidomimetic inhibitors of STAT3 protein","volume":"19","author":"Shahani","year":"2011","journal-title":"Bioorg Med Chem"},{"key":"10.1016\/j.bmcl.2026.130777_bb0095","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1073\/pnas.1424171112","article-title":"Suppression of cancer relapse and metastasis by inhibiting cancer stemness","volume":"112","author":"Li","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.bmcl.2026.130777_bb0100","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1158\/1535-7163.261.3.3","article-title":"Novel peptidomimetic inhibitors of signal transducer and activator of transcription 3 dimerization and biological activity","volume":"3","author":"Turkson","year":"2004","journal-title":"Mol Cancer Ther"},{"key":"10.1016\/j.bmcl.2026.130777_bb0105","doi-asserted-by":"crossref","first-page":"4700","DOI":"10.1073\/pnas.0409894102","article-title":"A low-molecular-weight compound discovered through virtual database screening inhibits Stat3 function in breast cancer cells","volume":"102","author":"Song","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.bmcl.2026.130777_bb0110","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/j.chembiol.2006.09.018","article-title":"Stattic: a small-molecule inhibitor of STAT3 activation and dimerization","volume":"13","author":"Schust","year":"2006","journal-title":"Chem Biol"},{"key":"10.1016\/j.bmcl.2026.130777_bb0115","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1097\/CAD.0b013e32832afc04","article-title":"Curcumin analogues exhibit enhanced growth suppressive activity in human pancreatic cancer cells","volume":"20","author":"Friedman","year":"2009","journal-title":"Anti-Cancer Drugs"},{"key":"10.1016\/j.bmcl.2026.130777_bb0120","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1021\/ml100010j","article-title":"Structure-based design of conformationally constrained, cell-permeable STAT3 inhibitors","volume":"1","author":"Chen","year":"2010","journal-title":"ACS Med Chem Lett"},{"key":"10.1016\/j.bmcl.2026.130777_bb0125","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1039\/B402431A","article-title":"Natural product based inhibitors of the thioredoxin-thioredoxin reductase system","volume":"2","author":"Wipf","year":"2004","journal-title":"Org Biomol Chem"},{"key":"10.1016\/j.bmcl.2026.130777_bb0130","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/s42003-022-03405-w","article-title":"Mitochondrial TrxR2 regulates metabolism and protects from metabolic disease through enhanced TCA and ETC function","volume":"5","author":"Chocron","year":"2022","journal-title":"Commun Biol"},{"key":"10.1016\/j.bmcl.2026.130777_bb0135","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1146\/annurev-pharmtox-052220-102509","article-title":"Thioredoxin reductase inhibition for Cancer therapy","volume":"62","author":"Gencheva","year":"2022","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"10.1016\/j.bmcl.2026.130777_bb0140","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.2174\/1871520617666170213150217","article-title":"Current progresses in metal-based anticancer complexes as mammalian TrxR inhibitors","volume":"17","author":"Cheng","year":"2017","journal-title":"Anti Cancer Agents Med Chem"},{"key":"10.1016\/j.bmcl.2026.130777_bb0145","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.phrs.2016.11.011","article-title":"Shikonin inhibits gefitinib-resistant non-small cell lung cancer by inhibiting TrxR and activating the EGFR proteasomal degradation pathway","volume":"115","author":"Li","year":"2017","journal-title":"Pharmacol Res"},{"key":"10.1016\/j.bmcl.2026.130777_bb0150","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.bcp.2015.12.004","article-title":"Inhibition of thioredoxin reductase by alantolactone prompts oxidative stress-mediated apoptosis of HeLa cells","volume":"102","author":"Zhang","year":"2016","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.bmcl.2026.130777_bb0155","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.freeradbiomed.2013.12.027","article-title":"Gambogic acid induces apoptosis in hepatocellular carcinoma SMMC-7721 cells by targeting cytosolic thioredoxin reductase","volume":"69","author":"Duan","year":"2014","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.bmcl.2026.130777_bb0160","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115191","article-title":"Tumor killing by a dietary curcumin mono-carbonyl analog that works as a selective ROS generator via TrxR inhibition","volume":"250","author":"Liu","year":"2023","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.bmcl.2026.130777_bb0165","doi-asserted-by":"crossref","first-page":"16132","DOI":"10.1021\/acs.jmedchem.1c01441","article-title":"Structural modification of aminophenylarsenoxides generates candidates for Leukemia treatment via thioredoxin reductase inhibition","volume":"64","author":"Song","year":"2021","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2026.130777_bb0170","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aax7945","article-title":"Irreversible TrxR1 inhibitors block STAT3 activity and induce cancer cell death","volume":"6","author":"Busker","year":"2020","journal-title":"Sci Adv"},{"key":"10.1016\/j.bmcl.2026.130777_bb0175","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.apsb.2023.11.004","article-title":"Trilogy of drug repurposing for developing cancer and chemotherapy-induced heart failure co-therapy agent","volume":"14","author":"Chen","year":"2024","journal-title":"Acta Pharm Sin B"},{"key":"10.1016\/j.bmcl.2026.130777_bb0180","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13321-018-0283-x","article-title":"ADMETlab: a platform for systematic ADMET evaluation based on a comprehensively collected database and 728 diverse models","volume":"10","author":"Dong","year":"2018","journal-title":"J Cheminform"}],"container-title":["Bioorganic & Medicinal Chemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X26002441?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X26002441?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:34:28Z","timestamp":1792067668000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960894X26002441"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2027,1]]},"references-count":36,"alternative-id":["S0960894X26002441"],"URL":"https:\/\/doi.org\/10.1016\/j.bmcl.2026.130777","relation":{},"ISSN":["0960-894X"],"issn-type":[{"value":"0960-894X","type":"print"}],"subject":[],"published":{"date-parts":[[2027,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of novel dual STAT3\/TrxR1 inhibitors via pharmacophore fusion as potent lead compounds for colorectal cancer","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmcl.2026.130777","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"130777"}}