{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T20:19:56Z","timestamp":1783628396163,"version":"3.55.0"},"reference-count":17,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T00:00:00Z","timestamp":1757808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2025,11,28]]},"abstract":"<jats:p>\n                    Malic enzyme 3 (ME3) plays a critical role in the survival of\n                    <jats:italic>SMAD4<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>\/ME2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    pancreatic ductal adenocarcinoma (PDAC) cells by supporting energy production and maintaining redox homeostasis. Therefore, targeting ME3 with small\u2010molecule inhibitors presents a promising therapeutic strategy for PDAC patients with\n                    <jats:italic>SMAD4\/ME2<\/jats:italic>\n                    deletions. Building upon our previously developed ME3 inhibitor, a systematic exploration of the structure\u2013activity relationship (SAR) was undertaken to identify novel chemotypes. This effort led to the discovery of a new series of indole\u2010substituted piperazine carboxamides with potent ME3 inhibitory activity, among which compound\n                    <jats:bold>13<\/jats:bold>\n                    emerged to be the most effective in PDAC cell lines. Furthermore, the synergistic effects of the newly identified compound\n                    <jats:bold>13<\/jats:bold>\n                    with the mitogen\u2010activated protein kinase kinase (MEK) inhibitor trametinib were evaluated on Hs766T cells which revealed a significant synergism of this combination.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500470","type":"journal-article","created":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T13:28:19Z","timestamp":1757856499000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Strategic Design and Development of Indole\u2010Based Compounds as Potent Malic Enzyme 3 Inhibitors for Pancreatic Tumor Therapy"],"prefix":"10.1002","volume":"20","author":[{"given":"Gaurav","family":"Sheth","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry Sun Pharma Advanced Research Company Ltd.  Vadodara 391775 India"},{"name":"Department of Chemistry Faculty of Science The Maharaja Sayajirao University of Baroda  Vadodara 390002 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4233-0449","authenticated-orcid":false,"given":"Shailesh R.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Science The Maharaja Sayajirao University of Baroda  Vadodara 390002 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabal","family":"Sengupta","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Sun Pharma Advanced Research Company Ltd.  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Vadodara 391775 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhav","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Discovery Sun Pharma Advanced Research Company Ltd.  Vadodara 391775 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Talwar","sequence":"additional","affiliation":[{"name":"Department of in vitro biology Sun Pharma Advanced Research Company Ltd.  Vadodara 391775 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinash","family":"Dhanave","sequence":"additional","affiliation":[{"name":"Department of in vitro biology Sun Pharma Advanced Research Company Ltd.  Vadodara 391775 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehul","family":"Raviya","sequence":"additional","affiliation":[{"name":"Department of in vitro biology Sun Pharma Advanced Research Company Ltd.  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