In vitro CAPE inhibitory activity towards human AKR1C3 and the molecular basis

被引：9
作者：
Li, Cuiyun [1 ,2 ]
Zhao, Yining [1 ,2 ]
Zheng, Xuehua [1 ,2 ]
Zhang, Hong [1 ,2 ]
Zhang, Liping [1 ,2 ]
Chen, Yunyun [1 ,2 ]
Li, Qing [1 ,2 ]
Hu, Xiaopeng [3 ]
机构：
[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Ctr Cellular & Struct Biol, Guangzhou 510006, Guangdong, Peoples R China
[3] Biopolcore Inc, Baltimore, MD USA
来源：
CHEMICO-BIOLOGICAL INTERACTIONS | 2016年 / 253卷
关键词：
CAPE; Octyl gallate; AKR1C3; Inhibition; Structure; KETO REDUCTASE SUPERFAMILY; PROSTAGLANDIN-F SYNTHASE; CAFFEIC ACID; PROSTATE-CANCER; SELECTIVE INHIBITORS; 17-BETA-HYDROXYSTEROID-DEHYDROGENASE AKR1C3; 1C3; ENZYME; POTENT; OVEREXPRESSION;
D O I：
10.1016/j.cbi.2016.05.012
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
AKR1C3 is a critical enzyme for producing testosterone and 5 alpha-DHT in the human body. Inhibiting AKR1C3 is a potential target for treating castration-resistant prostate cancer (CRPC). To find AKR1C3 inhibitors with a new molecular skeleton and binding mode, we analyzed the in vitro inhibitory activity of caffeic acid phenethyl ester (CAPE) and eight other phenolic acid analogues towards AKR1C3 and six other human AKR1 enzymes. We analyzed CAPE and octyl gallate interactions with AKR1C3 using X-ray crystallography, which provided a molecular basis for understanding the phenolic acid inhibitory activity and selectivity towards human AKR1s. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码：60 / 65
页数：6
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