title: In vitro CAPE inhibitory activity towards human AKR1C3 and the molecular basis.
abstract: AKR1C3 is a critical enzyme for producing testosterone and 5α-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.
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou, 510006, China.
authors.forename: Cuiyun
authors.initials: C
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou, 510006, China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou, 510006, China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Zheng
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou, 510006, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou, 510006, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou, 510006, China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou, 510006, China. Electronic address: liqing66@mail.sysu.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Biopolcore, Inc., Baltimore, MD, 21221, USA. Electronic address: xhu001@gmail.com.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Hu
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000074425:Aldo-Keto Reductase Family 1 Member C3; D001665:Binding Sites; D002109:Caffeic Acids / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D062385:Hydroxybenzoates / Q000737:chemistry / Q000378:metabolism*; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D002109:Caffeic Acids; D062385:Hydroxybenzoates; D020033:Protein Isoforms; D015096:3-Hydroxysteroid Dehydrogenases; D006911:Hydroxyprostaglandin Dehydrogenases; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3; C055494:caffeic acid phenethyl ester; C017616:phenolic acid; D010626:Phenylethyl Alcohol
keywords: AKR1C3; CAPE; Inhibition; Octyl gallate; Structure