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These compounds feature different linker lengths and cyclopropane modifications at the alkyne terminus. Computational studies showed that incorporating the cyclopropane group at the propargyl position facilitates the \u201cradical clock\u201d mechanism, achieving greater spatial separation and weaker orbital interactions between the two radical centers, thereby enhancing hydrogen abstraction ability. The PROTEC-4 compound exhibiting the strongest interaction with NAMPT, as demonstrated by docking studies, established significant cytotoxicity against human ovarian cancer A2780 cells with a half-inhibitory concentration (IC50) of 0.24 \u03bcM, indicating great potential for future antitumor drug development.<\/jats:p>","DOI":"10.1021\/acs.joc.6c01358","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T08:18:41Z","timestamp":1785140321000},"page":"10747-10752","source":"Crossref","is-referenced-by-count":1,"title":["Enediyne Chimeras\nfor Targeted NAMPT Degradation:\nEnhancing Cytotoxicity via a Radical Clock"],"prefix":"10.1021","volume":"91","author":[{"given":"Xiang","family":"Li","sequence":"first","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhengzhou University , , ,","place":["Zhengzhou, Henan Province, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7012-5621","authenticated-orcid":true,"given":"Yun","family":"Ding","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaming","family":"Lan","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-7269","authenticated-orcid":true,"given":"Aiguo","family":"Hu","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"2026080708082198400_cit1","article-title":"Chapter Eleven - Protein misfolding\nand its dual role in neurodegeneration and cancer progression","volume-title":"Advances in Protein Chemistry and Structural Biology","author":"Jamwal","year":"2025"},{"issue":"8","key":"2026080708082198400_cit2","doi-asserted-by":"publisher","first-page":"9686","DOI":"10.1007\/s12035-025-04838-0","article-title":"Advancements in Proteolysis Targeting\nChimeras for Targeted Therapeutic Strategies in Alzheimer\u2019s\nDisease","volume":"62","author":"Zhou","year":"2025","journal-title":"Mol. 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