| Inhibitors of mammalian acetyl-CoA carboxylase. | |
| | |
MedLine Citation:
|
PMID: 18221116 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Inhibition of acetyl-CoA carboxylase (ACC), with its resultant inhibition of fatty acid synthesis and stimulation of fatty acid oxidation, has the potential to favorably affect, in a concerted manner, a multitude of the cardiometabolic risk factors associated with diabetes, obesity, and the metabolic syndrome. Studies in ACC2 knockout mice and in experimental animals treated with isozyme-specific antisense oligonucleotides or with isozyme-nonselective ACC inhibitors have demonstrated the potential for treating metabolic syndrome through this modality. Co-crystallization of the biotin carboxylase and carboxyltransferase domains of eukaryotic ACC in the presence of substrates and inhibitors has revealed characteristics of the catalytic center that can be exploited in drug discovery. A variety of structurally diverse, mechanistically distinct classes of ACC inhibitors have been disclosed in the scientific and patent literature. Isozyme-nonselective ACC inhibitors may provide the optimal therapeutic potential. However, demonstration of the full potential of isozyme-selective inhibitors, once identified, should reveal advantages and liabilities associated with single isozyme inhibition. |
| | |
Authors:
|
Jeffrey W Corbett; James H Harwood |
Related Documents
:
|
11281196 - Isolation and preliminary characterization of the medium-chain fatty acid:coa ligase re... 2688746 - The oxidation of dicarboxylic acid coa esters via peroxisomal fatty acyl-coa oxidase. 7096336 - Alkyldihydroxyacetone-p synthase. solubilization, partial purification, new assay metho... 14992586 - Liver fatty acid-binding protein colocalizes with peroxisome proliferator activated rec... 22733276 - Quantitative imaging of electron transfer flavoprotein autofluorescence reveals the dyn... 6885696 - Gas-liquid chromatographic determination of dehydroacetic acid in squash and wine. |
Publication Detail:
|
Type: Journal Article; Review |
Journal Detail:
|
Title: Recent patents on cardiovascular drug discovery Volume: 2 ISSN: 1574-8901 ISO Abbreviation: Recent Pat Cardiovasc Drug Discov Publication Date: 2007 Nov |
Date Detail:
|
Created Date: 2008-01-28 Completed Date: 2008-02-25 Revised Date: 2011-11-10 |
Medline Journal Info:
|
Nlm Unique ID: 101263805 Medline TA: Recent Pat Cardiovasc Drug Discov Country: United Arab Emirates |
Other Details:
|
Languages: eng Pagination: 162-80 Citation Subset: IM |
Affiliation:
|
Pfizer Global Research & Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. jeffrey.w.corbett@pfizer.com |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acetyl-CoA Carboxylase
/
antagonists & inhibitors*,
metabolism Animals Diabetes Mellitus / drug therapy, enzymology Drug Design Enzyme Inhibitors / pharmacology*, therapeutic use Heart Diseases / drug therapy, enzymology Humans Isoenzymes / antagonists & inhibitors, metabolism Metabolic Syndrome X / drug therapy, enzymology Mice Obesity / drug therapy, enzymology Rats |
| Chemical | |
Reg. No./Substance:
|
0/Enzyme Inhibitors; 0/Isoenzymes; EC 6.4.1.2/Acetyl-CoA Carboxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Nebivolol: more than a highly selective Beta blocker.
Next Document: Cilostazol: a new drug in the treatment intermittent claudication.