Inhibition of human α-methylacyl CoA racemase (AMACR): a target for prostate cancer.
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.
Department of Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool L69 7ZD (UK). acarnell@liv.ac.uk.
Andrew J
AJ
Carnell
Ralph
R
Kirk
Matthew
M
Smith
Shane
S
McKenna
Lu-Yun
LY
Lian
Robert
R
Gibson
D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D019998:Racemases and Epimerases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
D004791:Enzyme Inhibitors; D013859:Thiocarbamates; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase
AMACR; MCR; coenzyme A; inhibitors; α‐methylacyl CoA racemase