Inhibition of Human α‐Methylacyl CoA Racemase (AMACR): a Target for Prostate Cancer |
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| Authors: | Dr. Andrew J. Carnell Ralph Kirk Matthew Smith Shane McKenna Prof. Lu‐Yun Lian Dr. Robert Gibson |
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| Affiliation: | 1. Department of Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool L69 7ZD (UK);2. Institute of Integrative Biology, Biosciences Building, University of Liverpool, Crown Street, Liverpool L69 7ZB (UK) |
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| Abstract: | The enzyme α‐methylacyl CoA racemase (AMACR) is involved in the metabolism of branched‐chain fatty acids and has been identified as a promising therapeutic target for prostate cancer. By using the recently available human AMACR from HEK293 kidney cell cultures, we tested a series of new rationally designed inhibitors to determine the structural requirements in the acyl component. An N‐methylthiocarbamate (Ki=98 nM ), designed to mimic the proposed enzyme‐bound enolate, was found to be the most potent AMACR inhibitor reported to date. |
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| Keywords: | AMACR coenzyme A inhibitors MCR α ‐methylacyl CoA racemase |
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