Document Detail


Fenofibrate but not fenofibric acid inhibits 11beta-hydroxysteroid dehydrogenase 1 in C2C12 myotubes.
MedLine Citation:
PMID:  20614230     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Fibrates and WY-14643 are widely used as lipid-lowering drugs via modulation of peroxisome proliferator-activated receptor alpha (PPAR α) for the treatment of a wide range of metabolic disorders. Here, to address the question whether PPAR α agonists can affect the enzymatic activity of 11beta-hydroxysteroid dehydrogenase1 (11β-HSD1), we tested fibrates and WY-14643 for the inhibition of cellular 11β-HSD1 activity in C2C12 myotubes. Only fenofibrate but not fenofibric acid, an active agonist of PPAR α, exerted a potent inhibitory activity in the cell based assay, showing an IC(50) of 1.6 μM. Furthermore, we also demonstrated that the masking of carboxyl group in fenofibric acid via esterification or amidation was required for the inhibitory potencies of fenofibric acid derivatives against 11β-HSD1. In this presentation, we propose that fenofibrate can display a pharmacodynamic role distinct from fenofibric acid through masking of carboxyl group in fenofibric acid.
Authors:
Chi Hyun Kim; Ravirala Ramu; Jin Hee Ahn; Myung Ae Bae; Young Sik Cho
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-08
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  344     ISSN:  1573-4919     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  91-8     Citation Subset:  IM    
Affiliation:
Pharmacology Research Center, Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon, South Korea.
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