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This peptide shows the potential to specifically inhibit the function of MCL1, and demonstrates effective antitumor activity against several blood tumor cell lines with the half maximal inhibitory concentration (IC\n                    <jats:sub>50<\/jats:sub>\n                    ) values for cell-penetrating peptide-conjugated 5L1 in the range of 0.6 to 3 \u03bcM. Structural analysis revealed that it functions similarly to molecular glue, capable of binding to two MCL1 molecules simultaneously and inducing their homodimerization. This unique mechanism of action distinguishes it from traditional small-molecule MCL1 inhibitors, underscoring the potential of macrocyclic peptides functioning as molecular glues. Moreover, it inspires the development of highly selective inhibitors targeting MCL1 and other related targets with this glue-like mechanism.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2426006122","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T13:37:55Z","timestamp":1742909875000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":7,"title":["De novo discovery of a molecular glue\u2013like macrocyclic peptide that induces MCL1 homodimerization"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7143-4151","authenticated-orcid":false,"given":"Fengwei","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University","place":["Qingdao, China"]},{"name":"Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Shandong Energy 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