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• W1856945769 abstract "// Xiaoping Song 1 , Zhimin Zhao 1 , Xin Qi 1 , Shuai Tang 2 , Qiang Wang 3 , Tianjiao Zhu 1 , Qianqun Gu 1 , Ming Liu 1 , Jing Li 1 1 Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, P. R. China 2 Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China 3 Department of Pharmacy, School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, P. R. China Correspondence to: Ming Liu, e-mail: lmouc@hotmail.com Jing Li, e-mail: ljlilac@163.com Keywords: pipolythiodioxopiperazines, HDN-1, chaetocin, inhibitor, Hsp90 Received: September 28, 2014      Accepted: January 01, 2015      Published: January 24, 2015 ABSTRACT 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 Hsp90α, resulting in a potential conformational change that interfered with the binding of 17-AAG and novobiocin to Hsp90α. In contrast, association of 17-AAG, novobiocin or ATP with Hsp90α did not prevent the binding HDN-1 to Hsp90α. 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 Hsp90α 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." @default.
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• W1856945769 date "2015-01-24" @default.
• W1856945769 modified "2023-10-03" @default.
• W1856945769 title "Identification of epipolythiodioxopiperazines HDN-1 and chaetocin as novel inhibitor of heat shock protein 90" @default.
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• W1856945769 doi "https://doi.org/10.18632/oncotarget.3029" @default.
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