{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T16:09:03Z","timestamp":1791130143464,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA2333959"],"award-info":[{"award-number":["R01 CA2333959"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA247232"],"award-info":[{"award-number":["R01 CA247232"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,8,27]]},"abstract":"<jats:p>\n                    REV7 is an adaptor protein that mediates protein\u2013protein interactions (PPIs) in DNA damage response and cell cycle control. REV7 functions as a subunit of the translesion synthesis (TLS) DNA polymerase POL\u03b6, which is involved in the replicative bypass of DNA lesions. REV7 is also a component of the shieldin complex, which mediates the choice of pathway for DNA double\u2010stranded break (DSB) repair. TLS promotes cancer cell survival after DNA damage and serves as a mechanism through which cancers develop acquired chemoresistance. DSB repair helps cancers mitigate DNA breaks induced by radiation; therefore, inhibition of REV7 PPIs has emerged as a therapeutic strategy. We performed a docking\u2010based virtual screen to identify compounds predicted to disrupt PPIs between REV7 and the REV7\u2010binding motifs (RBMs) found in the REV3 subunit of POL\u03b6 (TLS) and the SHLD3 subunit of shieldin (DSB repair). Biochemical analysis of a promising hit compound and several analogues demonstrated the ability of this scaffold to disrupt the REV7\/RBM\n                    <jats:sub>REV3<\/jats:sub>\n                    PPI. Several REV7 inhibitors sensitize human cancer cells to radiation treatment, identifying these compounds as a new class of TLS and DSB\u2010repair targeted anticancer drugs with potential as adjuvant therapies to improve the efficacy of genotoxic cancer therapies.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70427","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:30:13Z","timestamp":1787200213000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Docking\u2010Based Virtual Screening Identifies a Small\u2010Molecule Inhibitor of the Translesion Synthesis REV7\/REV3 Protein\u2013Protein Interaction"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9958-4717","authenticated-orcid":false,"given":"Noah J.","family":"Harrahill","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seema M.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0696-4962","authenticated-orcid":false,"given":"Radha Charan","family":"Dash","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M.","family":"Zaino","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9007-165X","authenticated-orcid":false,"given":"Vihit","family":"Gupta","sequence":"additional","affiliation":[{"name":"University of Vermont Cancer Center and Department of Microbiology and Molecular Genetics University of Vermont  Burlington Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1861-0515","authenticated-orcid":false,"given":"Dane H.","family":"Geddes\u2010Buehre","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biophysics University of Connecticut Health Center  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6514-0290","authenticated-orcid":false,"given":"Colin","family":"Brereton","sequence":"additional","affiliation":[{"name":"University of Vermont Cancer Center and Department of Microbiology and Molecular Genetics University of Vermont  Burlington Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro A.","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biophysics University of Connecticut Health Center  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6556-9423","authenticated-orcid":false,"given":"Nimrat","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"University of Vermont Cancer Center and Department of Microbiology and Molecular Genetics University of Vermont  Burlington Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3556-2447","authenticated-orcid":false,"given":"Dmitry M.","family":"Korzhnev","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biophysics University of Connecticut Health Center  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9482-1712","authenticated-orcid":false,"given":"M. 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