{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:57:39Z","timestamp":1790762259964,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["22507064"],"award-info":[{"award-number":["22507064"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022MH243"],"award-info":[{"award-number":["ZR2022MH243"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2023LZY008"],"award-info":[{"award-number":["ZR2023LZY008"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2025LSW009"],"award-info":[{"award-number":["ZR2025LSW009"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2025LMB029"],"award-info":[{"award-number":["ZR2025LMB029"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Epidermal growth factor receptor (EGFR) mutation\u2010mediated drug resistance represents a major clinical challenge in the treatment of non\u2010small cell lung cancer (NSCLC). In this study, the lead compound\n                    <jats:bold>XJ2\u20102<\/jats:bold>\n                    was identified through structure\u2010based virtual screening. It exhibited potent anti\u2010proliferative activity against both EGFR\n                    <jats:sup>Del19<\/jats:sup>\n                    mutant PC\u20109 cells and EGFR\n                    <jats:sup>L858R\/T790M<\/jats:sup>\n                    mutant H1975 cells, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.88\u2009\u00b1\u20090.12\u2009\u03bcM and 0.77\u2009\u00b1\u20090.09\u2009\u03bcM, respectively. Mechanistic studies have demonstrated that\n                    <jats:bold>XJ2\u20102<\/jats:bold>\n                    directly targets and binds to the EGFR, thereby effectively inhibiting EGFR phosphorylation and its downstream signaling pathways in both in\u00a0vitro and in\u00a0vivo models. In tumor\u2010bearing mouse models,\n                    <jats:bold>XJ2\u20102<\/jats:bold>\n                    significantly reduced tumor burden. Preclinical safety evaluation indicated that no treatment\u2010related toxicity was observed for\n                    <jats:bold>XJ2\u20102<\/jats:bold>\n                    at all tested doses. With its novel molecular scaffold and mutant\u2010selective inhibitory profile,\n                    <jats:bold>XJ2\u20102<\/jats:bold>\n                    represents a promising lead compound for overcoming NSCLC drug resistance and advancing the development of next\u2010generation EGFR inhibitors.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70391","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T07:29:05Z","timestamp":1789111745000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of Potent\n                    <scp>EGFR<\/scp>\n                    Inhibitors for Del19 and\n                    <scp>L858R<\/scp>\n                    \/\n                    <scp>T790M<\/scp>\n                    Mutants Through Structure\u2010Based Virtual Screening and Biological Evaluation"],"prefix":"10.1111","volume":"108","author":[{"given":"Ting","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pharmacy (Shandong Provincial Key Traditional Chinese Medical Discipline of Clinical Chinese Pharmacy), Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (Shandong Provincial Key Traditional Chinese Medical Discipline of Clinical Chinese Pharmacy), Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (Shandong Provincial Key Traditional Chinese Medical Discipline of Clinical Chinese Pharmacy), Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Zuo","sequence":"additional","affiliation":[{"name":"Taian Central Hospital General ICU Zone 2  Taian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanshuang","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (Shandong Provincial Key Traditional Chinese Medical Discipline of Clinical Chinese Pharmacy), Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuguo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (Shandong Provincial Key Traditional Chinese Medical Discipline of Clinical Chinese Pharmacy), Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4775-0143","authenticated-orcid":false,"given":"Chuanfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (Shandong Provincial Key Traditional Chinese Medical Discipline of Clinical Chinese Pharmacy), Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (Shandong Provincial Key Traditional Chinese Medical Discipline of Clinical Chinese Pharmacy), Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.117178"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3048"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01310"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02554-7"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010022\u201000639\u20109"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21412"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.051"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0306430"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.117677"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.198"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm030644s"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112995"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00798-3"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909530"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/157340911795677602"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1612674"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00964"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.05.027"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw611"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1022"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx704"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/S12094-010-0473-0"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113705"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2088"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050753"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-018-0778-0"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3854"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2304594"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx703"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2010.97"},{"issue":"11","key":"e_1_2_10_32_1","article-title":"Optimal 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