Identification of epipolythiodioxopiperazines HDN-1 and chaetocin as novel inhibitor of heat shock protein 90

doi:10.18632/oncotarget.3029

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Identification of epipolythiodioxopiperazines HDN-1 and chaetocin as novel inhibitor of heat shock protein 90
	Song, Xiaoping 1; Zhao, Zhimin 1; Qi, Xin 1; Tang, Shuai 2; Wang, Qiang 3; Zhu, Tianjiao 1; Gu, Qianqun 1; Liu, Ming 1; Li, Jing1
刊名	ONCOTARGET
	2015-03-10
卷号	6 期号:7 页码:5263-5274
关键词	pipolythiodioxopiperazines HDN-1 chaetocin inhibitor Hsp90
ISSN号	1949-2553
DOI	10.18632/oncotarget.3029
文献子类	Article
英文摘要	The molecular chaperone heat shock protein 90 (Hsp90) has emerged as an important target for cancer treatment. HDN-1, an epipolythiopiperazine-2, 5-diones (ETPs) compound, was here identified as a new Hsp90 inhibitor. HDN-1 bound directly to C-terminus of Hsp90 alpha, resulting in a potential conformational change that interfered with the binding of 17-AAG and novobiocin to Hsp90 alpha. In contrast, association of 17-AAG, novobiocin or ATP with Hsp90 alpha did not prevent the binding HDN-1 to Hsp90 alpha. HDN-1 in combination with 17-AAG exhibited an enhanced inhibitory effect on non-small lung cancer cell proliferation. Molecular docking analyses revealed that HDN-1 bound to Hsp90 alpha at C-terminal 526-570 region. In addition, HDN-1 degraded multiple oncoproteins and promoted EGF-induced wild type and mutated EGFR downregulation. Notably, chaetocin, used as a SUV39H1 inhibitor with similar structure to HDN-1, bound to Hsp90 and degraded Hsp90 client proteins and SUV39H1 as did HDN-1. These results indicate that HDN-1 and chaetocin are inhibitors of Hsp90 and that SUV39H1 is a novel client protein of Hsp90.
资助项目	NSFC-Shandong Joint Fund[U1406402] ; Natural Science Foundation of China[81373323]
WOS关键词	C-TERMINAL DOMAIN ; MOLECULAR CHAPERONE ; CANCER-THERAPY ; BINDING POCKET ; ATP-BINDING ; HSP90 ; HEAT-SHOCK-PROTEIN-90 ; GELDANAMYCIN ; SENSITIVITY ; RESISTANCE
WOS研究方向	Oncology ; Cell Biology
语种	英语
出版者	IMPACT JOURNALS LLC
WOS记录号	WOS:000352792000051
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276610]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Liu, Ming
作者单位	1.Ocean Univ China, Sch Med & Pharm, Key Lab Marine Drugs, Minist Educ, Qingdao, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 200031, Peoples R China; 3.South Cent Univ Nationalities, Dept Pharm, Sch Pharmaceut Sci, Wuhan, Peoples R China
推荐引用方式 GB/T 7714	Song, Xiaoping,Zhao, Zhimin,Qi, Xin,et al. Identification of epipolythiodioxopiperazines HDN-1 and chaetocin as novel inhibitor of heat shock protein 90[J]. ONCOTARGET,2015,6(7):5263-5274.
APA	Song, Xiaoping.,Zhao, Zhimin.,Qi, Xin.,Tang, Shuai.,Wang, Qiang.,...&Li, Jing.(2015).Identification of epipolythiodioxopiperazines HDN-1 and chaetocin as novel inhibitor of heat shock protein 90.ONCOTARGET,6(7),5263-5274.
MLA	Song, Xiaoping,et al."Identification of epipolythiodioxopiperazines HDN-1 and chaetocin as novel inhibitor of heat shock protein 90".ONCOTARGET 6.7(2015):5263-5274.