{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:39:24Z","timestamp":1786977564235,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2017,10,4]],"date-time":"2017-10-04T00:00:00Z","timestamp":1507075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"the Institute of Medical Science, the University of Tokyo","award":["2016-2014"],"award-info":[{"award-number":["2016-2014"]}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2017,12,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Despite various inhibitors targeting the zinc center(s) of enzymes, drugs that target zinc fingers have not been examined in detail. We previously developed a dithiol compound named SN\u20101 that has an inhibitory effect on the function of zinc finger transcription factors, but its mechanism of action has not yet been elucidated. To establish a general principle for new drugs, the details of the action of SN\u20101 against a zinc finger protein were examined. As a zinc\u2010finger\u2010containing protein, we focused on TRAF6, which is related to cancer and inflammation. Binding of SN\u20101 to TRAF6 and its effect on TRAF6 ubiquitination were examined in\u2005vitro, and the binding mode was calculated by computational methodology. Furthermore, ubiquitination of TRAF6 and downstream signaling was examined by cell\u2010based experiments. The results show that SN\u20101 binds to TRAF6, inhibiting its auto\u2010ubiquitination and downstream NF\u2010\u03baB signaling. Docking studies indicate that SN\u20101 binds directly to the first zinc finger of TRAF6. This binding disrupts the neighboring structure, that is, the RING finger domain, to suppress the ubiquitin ligase activity of TRAF6. Taken together, this study provides a platform for developing new small molecules that target zinc finger proteins.<\/jats:p>","DOI":"10.1002\/cmdc.201700399","type":"journal-article","created":{"date-parts":[[2017,9,8]],"date-time":"2017-09-08T06:57:23Z","timestamp":1504853843000},"page":"1935-1941","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A Dithiol Compound Binds to the Zinc Finger Protein TRAF6 and Suppresses Its Ubiquitination"],"prefix":"10.1002","volume":"12","author":[{"given":"Ryoko","family":"Koga","sequence":"first","affiliation":[{"name":"Department of Bioorganic Medicinal Chemistry Faculty of Life Sciences Kumamoto University  Chuo-ku 862-0973 Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed O.","family":"Radwan","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Medicinal Chemistry Faculty of Life Sciences Kumamoto University  Chuo-ku 862-0973 Kumamoto Japan"},{"name":"Department of Chemistry of Natural Compounds National Research Center  12622 Dokki Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Ejima","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Medicinal Chemistry Faculty of Life Sciences Kumamoto University  Chuo-ku 862-0973 Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Kanemaru","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Medicinal Chemistry Faculty of Life Sciences Kumamoto University  Chuo-ku 862-0973 Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tateishi","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Medicinal Chemistry Faculty of Life Sciences Kumamoto University  Chuo-ku 862-0973 Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha F. 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