{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:01:42Z","timestamp":1785484902890,"version":"3.56.0"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Aberrant protein\u2013protein interactions (PPIs) play crucial roles in cancer progression by driving transcriptional repression and epigenetic silencing. Among these, the TRIM28\u2013EZH2 interaction is central to maintaining repressive chromatin states that promote tumorigenesis. In this study, we modeled the TRIM28\u2013EZH2 complex using protein\u2013protein docking, revealing a stable interface dominated by the RBCC domain of TRIM28 and the PRC2 catalytic domain of EZH2. A cysteine\u2010focused covalent inhibitor library was screened to identify small molecules capable of targeting reactive cysteines at the interface. Four lead compounds were identified, with compound C87 exhibiting the most favorable binding free energy (\u0394\n                    <jats:italic>G<\/jats:italic>\n                    <jats:sub>bind<\/jats:sub>\n                    \u00a0=\u00a0\u221257.2\u00a0kcal\/mol) and stable interactions throughout molecular dynamics simulations. These findings highlight the potential of covalent inhibition as a novel strategy to disrupt oncogenic TRIM28\u2013EZH2 complexes and restore tumor suppressor gene expression.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202502892","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T11:31:34Z","timestamp":1767871894000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting the TRIM28\u2013EZH2 Protein\u2013Protein Interface With Cysteine\u2010Reactive Covalent Inhibitors: A Computational Blueprint for Cancer Therapy"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9425-0267","authenticated-orcid":false,"given":"Ibrahim Oluwatobi","family":"Kehinde","sequence":"first","affiliation":[{"name":"Molecular Bio\u2010Computation and Drug Design Laboratory, School of Health Sciences University of KwaZulu\u2010Natal  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vuyisa","family":"Mzozoyana","sequence":"additional","affiliation":[{"name":"School of Chemistry and Physics, Westville Campus University of KwaZulu\u2010Natal  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sizwe J.","family":"Zamisa","sequence":"additional","affiliation":[{"name":"School of Chemistry and Physics, Westville Campus University of KwaZulu\u2010Natal  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mbuso","family":"Faya","sequence":"additional","affiliation":[{"name":"Discipline of Pharmaceutical Sciences College of Health Sciences University of KwaZulu\u2010Natal  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8711-7783","authenticated-orcid":false,"given":"Mahmoud E. 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