{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:12:01Z","timestamp":1788448321534,"version":"build-2803163510"},"reference-count":28,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Dose-Response"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>HER2 overexpression is almost invariably associated with advanced breast cancer disease and poor prognosis, hence its extensive review. This study therefore aims to discover and analyze potential HER2 inhibitors through computational methods to advance drug discovery and optimization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>A ligand-based virtual screening (LBVS) approach was employed to screen compounds from the ChEMBL database. From 8900 initial matches, 39 candidate compounds were selected based on structural similarity and ADME properties. Molecular docking was performed to assess binding affinity with HER2, followed by molecular dynamics (MD) simulations to evaluate complex stability. Additionally, a QSAR (quantitative structure-activity relationship) model was established to elucidate key structural features influencing inhibitory activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Five lead compounds were prioritized based on strong docking scores (&lt;\u22128.4\u00a0kcal\/mol). Among them, compound 2048788 (\u221211.0\u00a0kcal\/mol, predicted pIC\n                      <jats:sub>50<\/jats:sub>\n                      \u2248 8.6) and compound 3956509 (pIC\n                      <jats:sub>50<\/jats:sub>\n                      \u2248 8.4) showed superior binding affinity and pharmacokinetic properties compared to FDA-approved drugs (doxorubicin, letrozole, lanatuzumab). MD simulations confirmed complex stability. The initial QSAR model showed low predictive power (R\n                      <jats:sup>2<\/jats:sup>\n                      = 0.18, RMSE = 1.19), but after feature selection, performance improved significantly (RMSE = 0.57). Key positive contributors included hydrogen bond donor count (r = 0.63), lipophilicity (LogP, r = 0.60), and sp\n                      <jats:sup>3<\/jats:sup>\n                      carbon fraction (r =0.60), while excessive polarity and aromaticity reduced activity. Compounds within the 450-500\u00a0Da molecular weight range exhibited the highest activity (pIC\n                      <jats:sub>50<\/jats:sub>\n                      = 8.0-8.6).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study integrated virtual screening, docking, MD simulations, and QSAR modeling to identify compound 2048788 as a highly promising HER2 inhibitor. These findings provide a strong foundation for further optimization and the preclinical development of targeted HER2 therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15593258251394191","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T12:40:11Z","timestamp":1763383211000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring the Therapeutic Potential of Virtual Screened Novel HER2 Inhibitors via QSAR, Molecular Docking and Dynamics Simulations"],"prefix":"10.1177","volume":"23","author":[{"given":"Khurram","family":"Rehman","sequence":"first","affiliation":[{"name":"Gomal University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6973-6280","authenticated-orcid":false,"given":"Zoya","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqin","family":"Deng","sequence":"additional","affiliation":[{"name":"Hand and Foot Surgery Department, Shenzhen Second People\u2019s Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hina","family":"Ayub","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Gomal Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naseem","family":"Saba","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Gomal Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rida","family":"Asghar","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Gomal Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Shabbir","sequence":"additional","affiliation":[{"name":"The University of Lahore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencui","family":"Li","sequence":"additional","affiliation":[{"name":"Hand and Foot Surgery Department, Shenzhen Second People\u2019s Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.09.012"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2023.188871"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2022.110401"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15133468"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-023-02111-9"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14184543"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/10406638.2021.1942933"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-024-03251-x"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2025.141708"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202400182"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40199-023-00484-w"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1544"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2020.107591"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph16010120"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25204723"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201600182"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1074"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21707"},{"key":"e_1_3_5_20_2","unstructured":"Landrum G (2016). 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