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A chemical genomics approach to drug reprofiling in oncology : antipsychotic drug risperidone as a potential adenocarcinoma treatment
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Dilly, Suzanne J., Clark, Andrew J., Marsh, Andrew, Mitchell, Daniel A., Cain, Ricky, Fishwick, Colin W. G. and Taylor, Paul C. (2017) A chemical genomics approach to drug reprofiling in oncology : antipsychotic drug risperidone as a potential adenocarcinoma treatment. Cancer Letters, 393 . pp. 16-21. doi:10.1016/j.canlet.2017.01.042 ISSN 0304-3835.
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Official URL: http://dx.doi.org/10.1016/j.canlet.2017.01.042
Abstract
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-β-HSD10, a proposed prostate cancer target. A computational study and enzyme inhibition assay with full length human 17-β-HSD10 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.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QD Chemistry R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Journal or Publication Title: | Cancer Letters | ||||||||
Publisher: | Elsevier Ireland Ltd. | ||||||||
ISSN: | 0304-3835 | ||||||||
Official Date: | 1 May 2017 | ||||||||
Dates: |
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Volume: | 393 | ||||||||
Page Range: | pp. 16-21 | ||||||||
DOI: | 10.1016/j.canlet.2017.01.042 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||
Date of first compliant deposit: | 30 October 2017 | ||||||||
Date of first compliant Open Access: | 8 February 2018 | ||||||||
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