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Due to its aberrant activity, it is frequently implicated in haematopoietic cancers and represents an attractive target for the development of therapeutics that antagonize its activity. A selective BCL\u20102 inhibitor, venetoclax, was approved for treating chronic lymphocytic leukaemia, acute myeloid leukemia, and other haematologic malignancies, validating BCL\u20102 as an anticancer target. Since then, alternative therapeutic approaches to modulate the activity of BCL\u20102 have been explored, such as antibody\u2010drug conjugates and proteolysis\u2010targeting chimeras. Despite numerous research groups focusing on developing degraders of BCL\u20102 family member proteins, selective BCL\u20102 PROTACs remain elusive, as disclosed compounds only show dual BCL\u2010x\n                    <jats:sub>L<\/jats:sub>\n                    \/BCL\u20102 degradation. Herein, we report our efforts to develop BCL\u20102 degraders by incorporating two BCL\u20102 binding moieties into chimeric compounds that aim to hijack one of three E3 ligases: CRBN, VHL, and IAPs. Even though our project did not result in obtaining a potent and selective BCL\u20102 PROTAC, our research will aid in understanding the narrow chemical space of BCL\u20102 degraders.\n                  <\/jats:p>","DOI":"10.1002\/chem.202400430","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T04:26:47Z","timestamp":1717129607000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Design, Synthesis, and Evaluation of BCL\u20102 Targeting PROTACs"],"prefix":"10.1002","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8090-4477","authenticated-orcid":false,"given":"Ale\u0161a","family":"Bricelj","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy University of Ljubljana  A\u0161ker\u010deva cesta\u20057 SI-1000 Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuen Lam","family":"Dora 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