CAS OpenIR  > 中科院上海应用物理研究所2011-2018年
Discovery of a novel small inhibitor RJ19 targeting to human Hsp90
Cao, HL; Lyu, KK; Liu, B; Li, J; He, JH
2017
Source PublicationNUCLEAR SCIENCE AND TECHNIQUES
ISSN1001-8042
Volume28Issue:10Pages:-
Subtype期刊论文
AbstractHeat shock protein 90 (Hsp90) can promote growth and proliferation of cancer cells by helping in folding, conformational maturation, and activation of various client proteins. Therefore, Hsp90 has been paid more attention to as an anticancer drug target. Reported Hsp90 inhibitors have several limitations such as poor solubility, limited bioavailability, and hepatotoxicity. Here, a novel small inhibitor RJ19 has been designed using fragment-based drug discovery and synthesized. Additionally, a crystal structure of Hsp90(N) -RJ19 was determined by X-ray diffraction (resolution limit, 2.0 angstrom, PDB code 4L90). The crystal structure of Hsp90(N)-RJ19 was analyzed in detail and compared with that of native Hsp90(N), Hsp90(N)-ATP, and Hsp90(N) -GDM, respectively. It was indicated that RJ19 interacted with Hsp90(N) at the ATP-binding pocket, which suggests that RJ19 may replace nucleotides to bind with Hsp90(N) to result in chaperone function failure of Hsp90. RJ19, therefore, has emerged as a promising anticancer lead compound. Rearrangement and displacement of L2 Loop in Hsp90(N)=-RJ19 play a key role in the function failure, which also makes the pocket wider and longer facilitating structure modification of RJ19 later. The complex crystal structure and interaction between RJ19 and Hsp90(N) provide a rational basis for the design and optimization of novel anticancer drugs.
KeywordShock-protein 90 Atp Hydrolysis Chaperone Identification Binding Design Agent
DOI10.1007/s41365-017-0300-1
WOS KeywordSHOCK-PROTEIN 90 ; ATP HYDROLYSIS ; CHAPERONE ; IDENTIFICATION ; BINDING ; DESIGN ; AGENT
Indexed BySCI
Language英语
WOS IDWOS:000411149700011
Citation statistics
Document Type期刊论文
Identifierhttp://ir.sinap.ac.cn/handle/331007/28610
Collection中科院上海应用物理研究所2011-2018年
Recommended Citation
GB/T 7714
Cao, HL,Lyu, KK,Liu, B,et al. Discovery of a novel small inhibitor RJ19 targeting to human Hsp90[J]. NUCLEAR SCIENCE AND TECHNIQUES,2017,28(10):-.
APA Cao, HL,Lyu, KK,Liu, B,Li, J,&He, JH.(2017).Discovery of a novel small inhibitor RJ19 targeting to human Hsp90.NUCLEAR SCIENCE AND TECHNIQUES,28(10),-.
MLA Cao, HL,et al."Discovery of a novel small inhibitor RJ19 targeting to human Hsp90".NUCLEAR SCIENCE AND TECHNIQUES 28.10(2017):-.
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