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A novel silicone derivative of natural osalmid (DCZ0858) exerts anti-multiple myeloma activity by promoting cell apoptosis and inhibiting cell cycle and mTOR signaling

文献类型：期刊论文

作者Bu, Wenxuan1,2; Li, Bo3; Feng, Lijin4; Feng, Qilin2; Hu, Ke1; Xu, Zhijian3; Wang, Yingcong2; Xi, Mengyu3; Wang, Houcai2; Yang, Guang2
刊名AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
出版日期2021
卷号13期号:10页码:11439-11449
ISSN号1943-8141
关键词Multiple myeloma DCZ0858 mTOR bone marrow microenvironment cell proliferation cell apoptosis
通讯作者Zhu, Weiliang(wlzhu@simm.ac.cn) ; Shi, Jumei(shijumei@tongji.edu.cn)
英文摘要Multiple myeloma (MM) is a malignant disease characterized by abnormal proliferation of clonal plasma cells. Based on the organic drug osalmid, the novel small molecule compound DCZ0858 was designed and synthesized for treating MM. DCZ0858 inhibited the proliferation and activity of MM cells and reduced colony formation. It also promoted the apoptosis of primary cells from patients with MM and cultured MM cell lines but had little effect on peripheral blood mononuclear cells in healthy people. Simultaneously, DCZ0858 activated caspase family proteins, blocked MM cells in G0/G1 phase, and reduced the expression of related cyclins CDK4/6 and CyclinD1. Moreover, DCZ0858 overcame the protective effect of the bone marrow microenvironment and effectively inhibited the activity of mTORC1 and mTORC2. Further, xenograft model experiments in mice showed that DCZ0858 significantly inhibited the proliferation and growth of tumors, with low drug toxicity. These results indicate that DCZ0858 has marked anti-MM activity and little effect on normal cells and tissues, making it a new candidate clinical drug for the treatment of MM.
WOS关键词BEVACIZUMAB ; SURVIVAL ; PET
资助项目National Natural Science Foundation of China[81670194] ; National Natural Science Foundation of China[81870158] ; National Natural Science Foundation of China[81900210] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002] ; Natural Science Foundation of Shanghai, China[19ZR1467800]
WOS研究方向Oncology ; Research & Experimental Medicine
语种英语
出版者E-CENTURY PUBLISHING CORP
WOS记录号WOS:000714690100013
源URL[http://119.78.100.183/handle/2S10ELR8/298677]  
专题中国科学院上海药物研究所
通讯作者Zhu, Weiliang; Shi, Jumei
作者单位1.Nanjing Med Univ, Nanjing 211100, Peoples R China
2.Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Hematol, 301 Yanchang Rd, Shanghai 200072, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
4.Tongji Univ, Shanghai Peoples Hosp 10, Dept Pathol, Sch Med, Shanghai 200072, Peoples R China
推荐引用方式
GB/T 7714		 Bu, Wenxuan,Li, Bo,Feng, Lijin,et al. A novel silicone derivative of natural osalmid (DCZ0858) exerts anti-multiple myeloma activity by promoting cell apoptosis and inhibiting cell cycle and mTOR signaling[J]. AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH,2021,13(10):11439-11449.
APA Bu, Wenxuan.,Li, Bo.,Feng, Lijin.,Feng, Qilin.,Hu, Ke.,...&Shi, Jumei.(2021).A novel silicone derivative of natural osalmid (DCZ0858) exerts anti-multiple myeloma activity by promoting cell apoptosis and inhibiting cell cycle and mTOR signaling.AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH,13(10),11439-11449.
MLA Bu, Wenxuan,et al."A novel silicone derivative of natural osalmid (DCZ0858) exerts anti-multiple myeloma activity by promoting cell apoptosis and inhibiting cell cycle and mTOR signaling".AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH 13.10(2021):11439-11449.

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来源：上海药物研究所

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