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Overexpression of Trip13 has been detected in many cancers and is associated with myeloma progression, disease relapse and poor prognosis inmultiple myeloma (MM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We have identified a small molecular, TI17, through a parallel compound\u2010centric approach, which specifically targets Trip13. To identify whether TI17 targeted Trip13, pull\u2010down and nuclear magnetic resonance spectroscopy (NMR) assays were performed. Cell counting kit\u20108, clone formation, apoptosis and cell cycle assays were applied to investigate the effects of TI17. We also utilized a mouse model to investigate the effects of TI17 in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TI17 effectively inhibited the proliferation of MM cells, and induced the cycle arrest and apoptosis of MM cells. Furthermore, treatment with TI17 abrogates tumor growth and has no apparent side effects in mouse xenograft models. TI17 specifically impaired Trip13 function of DSBs repair and enhanced DNA damage responses in MM. Combining with melphalan or HDAC inhibitor panobinostat triggers synergistic anti\u2010MM effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study suggests that TI17 could be acted as a specific inhibitor of Trip13 and supports a preclinical proof of concept for therapeutic targeting of Trip13 in MM.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.6706","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T09:46:52Z","timestamp":1699523212000},"page":"21321-21334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>TI17<\/scp>, a novel compound, exerts <scp>anti\u2010MM<\/scp> activity by impairing Trip13 function of <scp>DSBs<\/scp> repair and enhancing <scp>DNA<\/scp> damage"],"prefix":"10.1002","volume":"12","author":[{"given":"Shuaikang","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Hematology, Shanghai East Hospital 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