36986-31-9Relevant articles and documents
New molecular markers for prostate tumor imaging: A study on 2-methylene substituted fatty acids as new AMACR inhibitors
Morgenroth, Agnieszka,Urusova, Elizaveta A.,Dinger, Cornelia,Al-Momani, Ehab,Kull, Thomas,Glatting, Gerhard,Frauendorf, Holm,Jahn, Olaf,Mottaghy, Felix M.,Reske, Sven N.,Zlatopolskiy, Boris D.
, p. 10144 - 10150 (2011)
The development of prostate carcinoma is associated with alterations in fatty acid metabolism. α-Methylacyl-CoA racemase (AMACR) is a peroxisomal and mitochondrial enzyme that catalyses interconversion between the (S)/(R)-isomers of a range of α-methylacyl-CoA thioesters. AMACR is involved in the β-oxidation of the dietary branched-chain fatty acids and bile acid intermediates. It is highly expressed in prostate (more than 95 %), colon (92 %), and breast cancers (44 %) but not in the respective normal or hyperplastic tissues. Thus, targeting of AMACR could be a new strategy for molecular imaging and therapy of prostate and some other cancers. Unlabeled 2-methylenacyl-CoA thioesters (12 a-c) were designed as AMACR binding ligands. The thioesters were tested for their ability to inhibit the AMACR-mediated epimerization of (25R)-THC-CoA and were found to be strong AMACR inhibitors. Radioiodinated (E)-131I-13-iodo-2-methylentridec-12-enoic acid ( 131I-7 c) demonstrated preferential retention in AMACR-positive prostate tumor cells (LNCaP, LNCaP C4-2wt and DU145) compared with both AMACR-knockout LNCaP C4-2 AMACR-siRNA and benign BPH1 prostate cell lines. A significant protein-bound radioactive fraction with main bands at 47 (sum of molecular weights of AMACR plus 12 c), 70, and 75 kDa was detected in LNCaP C4-2 wt cells. Copyright
