{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:57:45Z","timestamp":1790927865612,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32401074"],"award-info":[{"award-number":["32401074"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The MYC oncogene is dysregulated in nearly 70% of human cancers and plays a central role in tumor initiation and progression. However, direct targeting of c\u2010MYC remains challenging because of its \u201cundruggable\u201d nature. Stabilization of DNA G\u2010quadruplex (G4) structures within the c\u2010MYC promoter offers an alternative strategy to suppress c\u2010MYC transcription. Here, we report the synthesis and biological evaluation of a series of styryl quinolinium ligands, identifying\n                    <jats:bold>PQB\u20104<\/jats:bold>\n                    as a selective c\u2010MYC DNA G4\u2010binder (\n                    <jats:italic>\n                      K\n                      <jats:sub>D<\/jats:sub>\n                    <\/jats:italic>\n                    &lt;1.0 \u00b5M).\n                    <jats:bold>PQB\u20104<\/jats:bold>\n                    exhibited marked antiproliferative activity against pancreatic cancer cell lines, including MIA PaCa\u20102 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a02.9 \u00b5M), PANC\u20101 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a04.5 \u00b5M), and gemcitabine\u2010resistant PANC\u20101 cells (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a05.0 \u00b5M), while showing substantially lower toxicity toward noncancerous HK\u20102 cells (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a040.1 \u00b5M). Mechanistically,\n                    <jats:bold>PQB\u20104<\/jats:bold>\n                    stabilized c\u2010MYC DNA G4\u2010structures, suppressed c\u2010MYC mRNA and protein expression, induced G0\/G1 cell\u2010cycle arrest, and activated a p53\u2010dependent DNA damage response.\n                    <jats:bold>PQB\u20104<\/jats:bold>\n                    also promoted telomere damage, cellular senescence, mitochondrial dysfunction, ferroptosis, and mitophagy, while inhibiting cancer cell migration, proliferation, and survival. Notably,\n                    <jats:bold>PQB\u20104<\/jats:bold>\n                    synergized strongly with gemcitabine in resistant PANC\u20101 cells (CI\u00a0=\u00a00.027). In a PANC\u20101 xenograft model,\n                    <jats:bold>PQB\u20104<\/jats:bold>\n                    reduced tumor weight by 44%. These findings highlight c\u2010MYC DNA G4 targeting by\n                    <jats:bold>PQB\u20104<\/jats:bold>\n                    as a feasible therapeutic strategy for pancreatic cancer, particularly in gemcitabine\u2010resistant disease.\n                  <\/jats:p>","DOI":"10.1002\/anie.8584442","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:49:41Z","timestamp":1790927381000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A DNA G\u2010Quadruplex\u2010Targeting Ligand Suppresses c\u2010MYC Expression: Implications for Gemcitabine\u2011Resistant Pancreatic Cancer"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0191-9719","authenticated-orcid":false,"given":"Bo\u2010Xin","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Life Sciences The Hong Kong Polytechnic University, Hung Hom  Kowloon Hong Kong SAR 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