Novel Triapine Derivative Induces Copper-Dependent Cell Death in Hematopoietic Cancers

doi:10.1021/acs.jmedchem.8b01996

	Novel Triapine Derivative Induces Copper-Dependent Cell Death in Hematopoietic Cancers
	Chen, Ge1,3,5,6,8 ; Niu, Chunyi 1; Yi, Jianhua 1; Sun, Lin 1; Cao, Hengyi 1,8; Fang, Yanjia 1; Jin, Taijie 1,8; Li, Ying 1; Lou, Chunli2,4 ; Kang, Jingwu 2; Wei, Wanguo3,7 ; Zhu, Jidong 1
	2019-03-28
发表期刊	JOURNAL OF MEDICINAL CHEMISTRY (IF:6.8[JCR-2023],7.1[5-Year])
ISSN	0022-2623
卷号	62 期号:6 页码:3107-3121
发表状态	已发表
DOI	10.1021/acs.jmedchem.8b01996
摘要	Triapine, an iron chelator that inhibits ribonucleotide reductase, has been evaluated in clinical trials for cancer treatment. Triapine in combination with other chemotherapeutic agents shows promising efficacy in certain hematologic malignancies; however, it is less effective against many advanced solid tumors, probably due to the unsatisfactory potency and pharmacokinetic properties. In this report, we developed a triapine derivative IC2S (10) with potent antitumor activity. 10 Preferentially inhibited the proliferation of hematopoietic cancers by inducing mitochondria reactive oxygen species production and mitochondrial dysfunction. Unlike triapine, 10 executed cytotoxic action in a copper-dependent manner. 10 Induced up-expression of thioredoxin-interacting protein resulted in decreased thioredoxin activity to permit c-Jun N-terminal kinase and p38 activation and ultimately led to the execution of the cell death program. Remarkedly, 10 showed good bioavailability and inhibited tumor growth in mouse xenograft models. Taken together, our study identifies compound 10 as a copper-dependent antitumor agent, which may be applied to the treatment of hematopoietic cancers.
收录类别	SCI ; SCIE ; IC
语种	英语
资助项目	Shanghai Scientific and Technological Innovation Project[17DZ1205400]
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Chemistry, Medicinal
WOS记录号	WOS:000463116900016
出版者	AMER CHEMICAL SOC
WOS关键词	RIBONUCLEOTIDE REDUCTASE INHIBITOR ; OXYGEN SPECIES GENERATION ; PHASE-I TRIAL ; OXIDATIVE STRESS ; IRON CHELATORS ; ADVANCED-STAGE ; MODULATION ; MECHANISMS ; APOPTOSIS ; LEUKEMIA
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/34173
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_魏万国组物质科学与技术学院_硕士生
通讯作者	Zhu, Jidong
作者单位	1.Chinese Acad Sci, Interdisciplinary Res Ctr Biol & Chem, Ctr Excellence Mol Synth, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Ctr Excellence Mol Synth, State Key Lab Bioorgan & Nat Prod Chem, Shanghai Inst Organ Chem, Shanghai 201203, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 4.ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai 201210, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Biochem, CAS Ctr Excellence Mol Cell Sci, Shanghai 200031, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Cell Biol, CAS Ctr Excellence Mol Cell Sci, Shanghai 200031, Peoples R China 7.Chinese Acad Sci, Shanghai Adv Res Inst, Shanghai 201210, Peoples R China 8.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
第一作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Chen, Ge,Niu, Chunyi,Yi, Jianhua,et al. Novel Triapine Derivative Induces Copper-Dependent Cell Death in Hematopoietic Cancers[J]. JOURNAL OF MEDICINAL CHEMISTRY,2019,62(6):3107-3121.
APA	Chen, Ge.,Niu, Chunyi.,Yi, Jianhua.,Sun, Lin.,Cao, Hengyi.,...&Zhu, Jidong.(2019).Novel Triapine Derivative Induces Copper-Dependent Cell Death in Hematopoietic Cancers.JOURNAL OF MEDICINAL CHEMISTRY,62(6),3107-3121.
MLA	Chen, Ge,et al."Novel Triapine Derivative Induces Copper-Dependent Cell Death in Hematopoietic Cancers".JOURNAL OF MEDICINAL CHEMISTRY 62.6(2019):3107-3121.