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Therefore, targeting the METTL3\/METTL14 complex represents a potential therapeutic approach for AML. Although several METTL3 inhibitors have been discovered, their SAM-competitive mode of action often results in reduced cellular potency, prompting interest in alternative strategies such as targeted protein degradation. In this article, we expand upon reported METTL3\/METTL14 complex degraders through exploration of CRBN-recruiting proteolysis-targeting chimeras (PROTACs) from multiple exit vectors of UZH2, a reported METTL3 inhibitor. The most potent PROTAC,\n                    <jats:bold>4j<\/jats:bold>\n                    , demonstrated sub-micromolar degradation potency in MV4.11 cells with DC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.44\u2009\u00b5M for METTL3 and 0.13\u2009\u00b5M for METTL14. Notably,\n                    <jats:bold>4j<\/jats:bold>\n                    showed enhanced cytotoxicity in MV4.11 cells compared to well-validated METTL3 inhibitors, underscoring the therapeutic potential of targeted degradation of the METTL3\/METTL14 complex in AML.\n                  <\/jats:p>","DOI":"10.1007\/s00044-025-03464-8","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T10:27:10Z","timestamp":1757068030000},"page":"2299-2308","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Discovery of CRBN-recruiting PROTAC degraders of the METTL3-METTL14 complex"],"prefix":"10.1007","volume":"34","author":[{"given":"Alexis R.","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rukiye","family":"Nar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Gour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhisheak","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangrong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5624-8003","authenticated-orcid":false,"given":"Zhixing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"3464_CR1","doi-asserted-by":"publisher","first-page":"7239","DOI":"10.1093\/nar\/gkab378","volume":"49","author":"S Oerum","year":"2021","unstructured":"Oerum S, Meynier V, Catala M, Tisn\u00e9 C. 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