Abstract | BACKGROUND AND PURPOSE: Finding new indications for existing drugs, also known as drug repositioning or repurposing, is a powerful approach to accelerate drug discovery and development. The unfolded protein response pathways have been proposed to be a viable target for developing new anticancer drugs. EXPERIMENTAL APPROACH: We screened the Johns Hopkins Drug Library for inhibitors of prostate cancer cell proliferation to identify new antiprostate cancer treatments among known drugs. We systematically investigated the mechanism underlying the anticancer activity of a hit and assessed its efficacy in blocking prostate tumour growth in a mouse model. KEY RESULTS: CONCLUSION AND IMPLICATIONS: Our findings revealed clofoctol as a novel activator of the unfolded protein response pathways and a promising inhibitor of prostate cancer. As clofoctol has been used in the clinic for years, it is ready for clinical evaluation as a novel antiprostate cancer drug candidate.
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Authors | Minghua Wang, Joong Sup Shim, Ruo-Jing Li, Yongjun Dang, Qingli He, Manisha Das, Jun O Liu |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 171
Issue 19
Pg. 4478-89
(Oct 2014)
ISSN: 1476-5381 [Electronic] England |
PMID | 24903412
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 The British Pharmacological Society. |
Chemical References |
- Anti-Bacterial Agents
- Antineoplastic Agents
- Chlorobenzenes
- Cresols
- DNA-Binding Proteins
- Regulatory Factor X Transcription Factors
- Transcription Factors
- clofoctol
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Topics |
- Animals
- Anti-Bacterial Agents
(pharmacology, therapeutic use)
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Cell Cycle
(drug effects)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Chlorobenzenes
- Cresols
(pharmacology, therapeutic use)
- DNA-Binding Proteins
(genetics)
- Humans
- Male
- Mice, Nude
- Prostatic Neoplasms
(drug therapy, metabolism, pathology)
- Regulatory Factor X Transcription Factors
- Transcription Factors
(genetics)
- Tumor Burden
(drug effects)
- Unfolded Protein Response
(drug effects)
- Xenograft Model Antitumor Assays
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