TI17, a novel compound, exerts anti-MM activity by impairing Trip13 function of DSBs repair and enhancing DNA damage
文献类型：期刊论文
| 作者 | Chang, Shuaikang7; Xiao, Wenqin6; Xie, Yongsheng5; Xu, Zhijian4 ; Li, Bo4; Wang, Guanli7; Hu, Ke7; Zhang, Yong4; Zhou, Jinfeng5; Song, Dongliang5
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| 刊名 | CANCER MEDICINE
 |
| 出版日期 | 2023-11-09 |
| 页码 | 14 |
| ISSN号 | 2045-7634 |
| 关键词 | DNA damage DSBs repair myeloma TI17 Trip13 |
| DOI | 10.1002/cam4.6706 |
| 通讯作者 | Lu, Yumeng(cao_ming_rain@sina.com) ; Shi, Jumei(shijumei@tongji.edu.cn) ; Zhu, Weiliang(wlzhu@simm.ac.cn) |
| 英文摘要 | Background: Thyroid hormone receptor interacting protein 13 (Trip13) is an AAA-ATPase that regulates the assembly or disassembly protein complexes and mediates Double-strand breaks (DSBs) repair. Overexpression of Trip13 has been detected in many cancers and is associated with myeloma progression, disease relapse and poor prognosis inmultiple myeloma (MM).Methods: We have identified a small molecular, TI17, through a parallel compound-centric approach, which specifically targets Trip13. To identify whether TI17 targeted Trip13, pull-down and nuclear magnetic resonance spectroscopy (NMR) assays were performed. Cell counting kit-8, 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.Results: 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-MM effect.Conclusions: 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. |
| WOS关键词 | MULTIPLE-MYELOMA ; CHECKPOINT ; RECOMBINATION ; PROTEIN ; PHOSPHORYLATION ; PROGRESSION ; ACTIVATION ; EXPRESSION ; BORTEZOMIB ; SIGNATURE |
| 资助项目 | We want to acknowledge Zhiqiang Li for the technical. |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| 出版者 | WILEY |
| WOS记录号 | WOS:001101928100001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/307634]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Lu, Yumeng; Shi, Jumei; Zhu, Weiliang |
| 作者单位 | 1.Tongji Univ, Shanghai Peoples Hosp 10, Dept Hematol, Sch Med, Shanghai 200072, Peoples R China 2.Shanghai East Hosp, Dept Hematol, 150 Jimo Rd, Shanghai 200120, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai, Peoples R China 5.Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Hematol, Shanghai, Peoples R China 6.Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Gastroenterol, Shanghai, Peoples R China 7.Tongji Univ, Sch Med, Dept Hematol, Shanghai East Hosp, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chang, Shuaikang,Xiao, Wenqin,Xie, Yongsheng,et al. TI17, a novel compound, exerts anti-MM activity by impairing Trip13 function of DSBs repair and enhancing DNA damage[J]. CANCER MEDICINE,2023:14. |
| APA | Chang, Shuaikang.,Xiao, Wenqin.,Xie, Yongsheng.,Xu, Zhijian.,Li, Bo.,...&Zhu, Weiliang.(2023).TI17, a novel compound, exerts anti-MM activity by impairing Trip13 function of DSBs repair and enhancing DNA damage.CANCER MEDICINE,14. |
| MLA | Chang, Shuaikang,et al."TI17, a novel compound, exerts anti-MM activity by impairing Trip13 function of DSBs repair and enhancing DNA damage".CANCER MEDICINE (2023):14. |
入库方式： OAI收割
来源：上海药物研究所
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