A chemical genomics approach to drug reprofiling in oncology: Antipsychotic drug risperidone as a potential adenocarcinoma treatment

被引：31

作者：

Dilly, Suzanne J. ^{[1
]}

Clark, Andrew J. ^{[2
]}

Marsh, Andrew ^{[2
]}

Mitchell, Daniel A. ^{[3
]}

Cain, Ricky ^{[4
]}

Fishwick, Colin W. G. ^{[4
]}

Taylor, Paul C. ^{[4
]}

机构：

[1] ValiRx Plc, 3rd Floor,16 Upper Woburn Pl, London WC1H 0BS, England

[2] Univ Warwick, Dept Chem, Coventry CV4 7AL, W Midlands, England

[3] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England

[4] Univ Leeds, Sch Chem, Leeds LS2 9JT, W Yorkshire, England

来源：

CANCER LETTERS | 2017年 / 393卷

基金：

英国生物技术与生命科学研究理事会;

关键词：

Chemical genomics; Drug reprofiling; Drosophila melanogaster; 17-beta-Hydroxysteroid dehydrogenase 10; Adenocarcinoma; ALZHEIMERS-DISEASE; ACCURATE DOCKING; CANCER; IDENTIFICATION; DROSOPHILA; DISCOVERY; THERAPEUTICS; INHIBITOR; GLIDE; CELLS;

D O I：

10.1016/j.canlet.2017.01.042

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Drug reprofiling is emerging as an effective paradigm for discovery of cancer treatments. Herein, an antipsychotic drug is immobilised using the Magic Tag chemical genomics tool and screened against a T7 bacteriophage displayed library of polypeptides from Drosophila melanogaster, as a whole genome model, to uncover an interaction with a section of 17-beta-HSD10, a proposed prostate cancer target. A computational study and enzyme inhibition assay with full length human 17-beta-FISD10 identifies risperidone as a drug reprofiling candidate. When formulated with rumenic acid, risperidone slows proliferation of PC3 prostate cancer cells in vitro and retards PC3 prostate cancer tumour growth in vivo in xenografts in mice, presenting an opportunity to reprofile risperidone as a cancer treatment. Crown Copyright (C) 2017 Published by Elsevier Ireland Ltd. All rights reserved.

引用

页码：16 / 21

页数：6

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