{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T04:12:12Z","timestamp":1745381532917,"version":"3.40.4"},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"8_Supplement_1","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,4,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Ubiquitin-Specific Protease 7 (USP7) is a member of one of the most largely studied families of deubiquitylating enzymes, proteases that play a key role in controlling the dynamics of ubiquitination within the cellular ubiquitome. USP7 plays a pivotal role in modulating the levels of multiple proteins, including tumor suppressors, transcription factors, epigenetic modulators, DNA repair proteins, and regulators of the immune response. This suggests USP7 as a promising druggable target that offers interesting new avenues for cancer therapy. Wherefore, the main goal of this study was the identification of promising small molecules that inhibit USP7 enzymatic activity. The work was conducted according to an integrated workflow combining Computer-Aided Drug Discovery (CADD) and High-Throughput Screening (HTS) of chemical libraries to discover and characterize selective USP7 inhibitors with new chemotypes and adequate pharmacological properties as potential drug candidates to be used for anticancer therapy. Such protocol screened a large set of databases, disclosing 9 novel USP7 hit compounds with in vitro USP7 inhibitory activities against both USP7 full-length and USP7 catalytic domain, displaying IC50 values between 4.5 \u03bcM to 33 \u03bcM. The dose-response curves of these compounds tested against cancer cell lines showed promising selective cytotoxicity in breast and lung cancer cells, with IC50 values ranging from low nanomolar to micromolar. These results highlight the utility of using CADD and HTS in the early steps of drug discovery and pave the way for the identification of novel USP7 inhibitors that might represent a steppingstone for cancer treatment.<\/jats:p>\n               <jats:sec>\n                  <jats:title>Citation Format:<\/jats:title>\n                  <jats:p>Rita I. Oliveira, Caio Franco, Miguel Mano, Ana Leal, Karen T. Liby, Jorge A. R. Salvador. Leveraging chemoinformatics and high-throughput screening for the identification of novel ubiquitin specific protease 7 (USP7) inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3165.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1158\/1538-7445.am2025-3165","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T12:11:36Z","timestamp":1745237496000},"page":"3165-3165","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract 3165: Leveraging chemoinformatics and high-throughput screening for the identification of novel ubiquitin specific protease 7 (USP7) inhibitors"],"prefix":"10.1158","volume":"85","author":[{"given":"Rita I.","family":"Oliveira","sequence":"first","affiliation":[{"name":"1Faculty of Pharmacy - University of Coimbra, Centre for Innovative Biomedicine and Biotechnology & Center for Neuroscience and Cell Biology - University of Coimbra, Coimbra, Portugal;"}]},{"given":"Caio","family":"Franco","sequence":"additional","affiliation":[{"name":"2Center for Neuroscience and Cell Biology - University of Coimbra, Coimbra, Portugal;"}]},{"given":"Miguel","family":"Mano","sequence":"additional","affiliation":[{"name":"3Centre for Innovative Biomedicine and Biotechnology & Center for Neuroscience and Cell Biology - University of Coimbra, Coimbra, Portugal, Coimbra, Portugal;"}]},{"given":"Ana","family":"Leal","sequence":"additional","affiliation":[{"name":"4IU School of Medicine, Indianapolis, IN."}]},{"given":"Karen T.","family":"Liby","sequence":"additional","affiliation":[{"name":"4IU School of Medicine, Indianapolis, IN."}]},{"given":"Jorge A. R.","family":"Salvador","sequence":"additional","affiliation":[{"name":"1Faculty of Pharmacy - University of Coimbra, Centre for Innovative Biomedicine and Biotechnology & Center for Neuroscience and Cell Biology - University of Coimbra, Coimbra, Portugal;"}]}],"member":"1086","container-title":["Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/85\/8_Supplement_1\/3165\/755988\/Abstract-3165-Leveraging-chemoinformatics-and-high","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/85\/8_Supplement_1\/3165\/755988\/Abstract-3165-Leveraging-chemoinformatics-and-high","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T05:34:51Z","timestamp":1745300091000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/85\/8_Supplement_1\/3165\/755988\/Abstract-3165-Leveraging-chemoinformatics-and-high"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,21]]},"references-count":0,"journal-issue":{"issue":"8_Supplement_1","published-print":{"date-parts":[[2025,4,21]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2025-3165","relation":{},"ISSN":["0008-5472","1538-7445"],"issn-type":[{"type":"print","value":"0008-5472"},{"type":"electronic","value":"1538-7445"}],"subject":[],"published":{"date-parts":[[2025,4,21]]}}}