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

- Demonstration that our Magic Tag® chemical genomics platform can be used to “reprofile” drugs into cancer indications.
- The use of fruit fly Drosophila melanogaster as an unusual model organism for cancer drug discovery.
- The further exploration of 17-β-hydroxysteroid dehydrogenase 10 as an emerging cancer target.
- The potential of VAL401 as a candidate for clinical trials in adenocarcinomas.

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.