{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T10:32:31Z","timestamp":1783938751481,"version":"3.55.0"},"reference-count":56,"publisher":"Wiley","issue":"29","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Concomitant inhibition of ataxia telangiectasia and Rad3\u2010related protein (ATR) and poly ADP\u2010ribose Polymerase (PARP) pathways is a promising strategy in cancer therapy, potentially expanding the clinical utility of ATR inhibitor (ATRi) and PARP inhibitor (PARPi). A novel series of ATR\/PARP1 dual inhibitors is developed through the pharmacophore fusion of AZD6738 and Olaparib. Among them,\n                    <jats:bold>B8<\/jats:bold>\n                    emerges as the most promising candidate, exhibiting potent ATR (IC\n                    <jats:sub>50<\/jats:sub>\n                    : 17.3\u00a0nM) and PARP1 (IC\n                    <jats:sub>50<\/jats:sub>\n                    : 0.38\u00a0nM) inhibition.\n                    <jats:bold>B8<\/jats:bold>\n                    effectively reduced cell viability, induced apoptosis, and caused G2\/M cell cycle arrest in TNBC cells. Additionally,\n                    <jats:bold>B8<\/jats:bold>\n                    significantly impaired TNBC colony formation, migration, and invasion. Mechanistically,\n                    <jats:bold>B8<\/jats:bold>\n                    induces DNA damage, evidenced by increased\n                    <jats:italic>\u03b3<\/jats:italic>\n                    H2AX levels. In in vivo studies,\n                    <jats:bold>B8<\/jats:bold>\n                    suppressed tumor growth more effectively than the combination in MDA\u2010MB\u2010468 xenografted mice, with no significant body weight loss.\n                    <jats:bold>B8<\/jats:bold>\n                    also enhanced\n                    <jats:italic>\u03b3<\/jats:italic>\n                    H2AX expression in tumor tissues. These findings confirm the synergistic effects of ATR\/PARP1 co\u2010inhibition and highlight the potential of this novel inhibitor class for TNBC therapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202501916","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T08:39:58Z","timestamp":1750063198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Novel ATR\/PARP1 Dual Inhibitors Demonstrate Synergistic Antitumor Efficacy in Triple\u2010Negative Breast Cancer Models"],"prefix":"10.1002","volume":"12","author":[{"given":"Yuan","family":"Gao","sequence":"first","affiliation":[{"name":"Clinical Research Institute Zhejiang Provincial People's Hospital (Affiliated People's Hospital) Hangzhou Medical College  Hangzhou Zhejiang Province 310000 China"},{"name":"School of Pharmacy Hangzhou Normal University  Hangzhou Zhejiang Province 310000 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Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese Medicines Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province Hangzhou Normal University  Hangzhou Zhejiang Province 310000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng\u2010Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Hangzhou Normal University  Hangzhou Zhejiang Province 310000 China"},{"name":"Key Laboratory of Elemene Class Anti\u2010Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese Medicines Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province Hangzhou Normal University  Hangzhou Zhejiang Province 310000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Zhejiang Provincial People's Hospital (Affiliated People\u2019 s Hospital) Hangzhou Medical College  Hangzhou Zhejiang Province 310000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo\u2010Wei","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Pharmacy Hangzhou Normal University  Hangzhou Zhejiang Province 310000 China"},{"name":"Key Laboratory of Elemene Class Anti\u2010Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese Medicines Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province Hangzhou Normal University  Hangzhou Zhejiang Province 310000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Qing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Hangzhou Normal University  Hangzhou Zhejiang Province 310000 China"},{"name":"Key Laboratory of Elemene Class Anti\u2010Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese Medicines Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province Hangzhou Normal University  Hangzhou Zhejiang Province 310000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng\u2010Hui","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Hangzhou Normal University  Hangzhou Zhejiang Province 310000 China"},{"name":"Key Laboratory of Elemene Class Anti\u2010Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese Medicines Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province Hangzhou Normal University  Hangzhou Zhejiang Province 310000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Science Hangzhou Normal University  Hangzhou Zhejiang Province 310000 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