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These mutations lead to dysregulation of hypoxia\u2010inducible factors (HIFs) and activation of oncogenic pathways, making VHL\u2010deficient ccRCC a challenging target for therapy. In this study, we identified cc\u2010885, a molecular glue degrader, as a selective inhibitor of VHL\u2010deficient ccRCC. cc\u2010885 promotes ubiquitination and degradation of transcription factor ETS1, which cooperates with EPAS1 (HIF\u20102\u03b1) to drive tumorigenesis. We demonstrated that cc\u2010885 selectively targeted the p51 and p42 isoforms of ETS1, disrupting p27\/p51 balance and suppressing ETS1 transcriptional activity. Moreover, combining cc\u2010885 with an EPAS1 inhibitor, belzutifan, significantly enhanced the anti\u2010tumor efficacy. Our findings provide a novel and precise therapeutic strategy for VHL\u2010deficient ccRCC by targeting ETS1 degradation and disrupting the ETS1\u2010EPAS1 complex.<\/jats:p>","DOI":"10.1002\/advs.202520237","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:04:46Z","timestamp":1778065486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Glue cc\u2010885 Inhibits VHL\u2010Deficient Clear Cell Renal Cell Carcinoma via ETS1 Degradation"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1827-2552","authenticated-orcid":false,"given":"Taowei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Urology The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong 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