European Journal of Medicinal Chemistry p. 63 - 73 (2017)
Update date:2022-07-29
Topics:
Wang, Lei
Li, Li
Zhou, Zi-Han
Jiang, Zheng-Yu
You, Qi-Dong
Xu, Xiao-Li
Identification of novel Hsp90 inhibitors to disrupt Hsp90-Cdc37 protein-protein interaction (PPI) could be an alternative strategy to achieve Hsp90 inhibition. In this paper, a series of small molecules targeting Hsp90-Cdc37 complex are addressed and characterized. The molecules' key characters are determined by utilizing a structure-based virtual screening workflow, derivatives synthesis, and biological evaluation. Structural optimization and structure–activity relationship (SAR) analysis were then carried out on the virtual hit of VS-8 with potent activity, which resulted in the discovery of compound 10 as a more potent regulator of Hsp90-Cdc37 interaction with a promising inhibitory effect (IC50?=?27?μM), a moderate binding capacity (KD?=?40?μM) and a preferable antiproliferative activity against several cancer lines including MCF-7, SKBR3 and A549?cell lines (IC50?=?26?μM, 15?μM and 38?μM respectively). All the data suggest that compound 10 exhibits moderate inhibitory effect on Hsp90-Cdc37 and could be regard as a first evidence of a non-natural compound targeting Hsp90-Cdc37 PPI.
View MoreTaixing Joxin Bio-tec Co.,Ltd.
website:http://www.joxbio.com
Contact:86-523-87558858 87612088
Address:No.88, chengdong industrial park
Contact:18669908765
Address:Zibo City, Shandong Province, P.R.China
Contact:+86-574- 87178138; 87297407
Address:No. 809, Liudingxingzuo, cangsong road, Ningbo, China
JOY (TIANJIN) TECHNOLOGY AND DEVELOPMENT CO., LTD.
Contact:+86-22-66666666
Address:Tianjin
Jinan Jinguilin Chemical Co.,Ltd
Contact:+86-531-81188412
Address:3rd floor of Torch Building, Huanyuan Rd, City of Jinan
Doi:10.1002/hlca.19770600626
(1977)Doi:10.1007/BF01518863
(1936)Doi:10.1016/0584-8539(80)80117-6
(1980)Doi:10.1021/jo00960a021
(1973)Doi:10.1021/ja01133a026
(1952)Doi:10.1021/jm00304a047
(1969)