{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T01:07:52Z","timestamp":1789348072582,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002461","name":"Chungbuk National University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002461","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102023\u2010NR076457"],"award-info":[{"award-number":["RS\u20102023\u2010NR076457"]}],"id":[{"id":"10.13039\/501100003725","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":[[2026,9,14]]},"abstract":"<jats:p>\n                    Triple\u2010negative breast cancer (TNBC) remains a major clinical challenge due to the absence of effective targeted therapies. In this study, thirty analogs of (\n                    <jats:italic>S<\/jats:italic>\n                    )\u20101\u2010oxo\u20101,2,3,4\u2010tetrahydropyrrolo[1,2\u2010\n                    <jats:italic>a<\/jats:italic>\n                    ]pyrazine\u20103\u2010carboxamide (\n                    <jats:bold>A1<\/jats:bold>\n                    \u2013\n                    <jats:bold>F5<\/jats:bold>\n                    ) were designed, synthesized, and evaluated for their cytotoxic activity against hormone receptor\u2010positive breast cancer (MCF\u20107) and EGFR\u2010overexpressing TNBC (MDA\u2010MB\u2010468) cell lines. Notably, compounds\n                    <jats:bold>B1<\/jats:bold>\n                    and\n                    <jats:bold>B3<\/jats:bold>\n                    exhibited potent growth inhibition toward MDA\u2010MB\u2010468 cells, with GI\n                    <jats:sub>50<\/jats:sub>\n                    values of 2.8 and 4.7\u2009\u00b5M, respectively, surpassing the efficacy of the reference compound (\n                    <jats:bold>Ref 2<\/jats:bold>\n                    , GI\n                    <jats:sub>50<\/jats:sub>\n                    : 7.6\u2009\u00b5M) and gefitinib (GI\n                    <jats:sub>50<\/jats:sub>\n                    : 16.5\u2009\u00b5M). Flow cytometric analysis demonstrated significant apoptosis induction by compounds\n                    <jats:bold>B1<\/jats:bold>\n                    and\n                    <jats:bold>B3<\/jats:bold>\n                    , with rates of 42.8% and 42.2%, respectively. Mechanistic investigations revealed that compounds\n                    <jats:bold>B1<\/jats:bold>\n                    and\n                    <jats:bold>B3<\/jats:bold>\n                    selectively inhibited Akt phosphorylation and enhanced JNK phosphorylation, suggesting a dual modulation of survival and apoptotic pathways. These findings support the development of\n                    <jats:italic>N2<\/jats:italic>\n                    \u2010benzyl\u2010(\n                    <jats:italic>S<\/jats:italic>\n                    )\u20101\u2010oxo\u20101,2,3,4\u2010tetrahydropyrrolo[1,2\u2010\n                    <jats:italic>a<\/jats:italic>\n                    ]pyrazine\u20103\u2010carboxamide analogs, particularly compound\n                    <jats:bold>B1<\/jats:bold>\n                    , as selective therapeutic candidates for triple\u2010negative breast cancer.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70463","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T01:35:09Z","timestamp":1787880909000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["(\n                    <i>S<\/i>\n                    )\u2010Pyrrolo[1,2\u2010\n                    <i>a<\/i>\n                    ]pyrazine\u20103\u2010carboxamide Analogs as Dual Akt\/JNK Modulators With Antiproliferative Effects in MDA\u2010MB\u2010468 Cells"],"prefix":"10.1002","volume":"21","author":[{"given":"Narges","family":"Hosseininasab","sequence":"first","affiliation":[{"name":"College of Pharmacy Chungbuk National University  Cheongju Chungbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sou Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy Research Institute for Drug Development Pusan National University  Busan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye\u2010Mi","family":"Kwon","sequence":"additional","affiliation":[{"name":"Development Center (NDDC) Daegu\u2010Gyeongbuk Medical Innovation Foundation (KMEDIhub)  Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungjin","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungbuk National University  Cheongju Chungbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanhyun","family":"Jung","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungbuk National University  Cheongju Chungbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwanghee","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungbuk National University  Cheongju Chungbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beom\u2010Jun","family":"Wi","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungbuk National University  Cheongju Chungbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su\u2010Jin","family":"Yoo","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungbuk National University  Cheongju Chungbuk Republic of 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