| 17(R),18(S)-epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: structure-activity relationships and stable analogues. | |
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MedLine Citation:
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PMID: 21591683 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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17(R),18(S)-epoxyeicosatetraenoic acid [17(R),18(S)-EETeTr], a cytochrome P450 epoxygenase metabolite of eicosapentaenoic acid (EPA), exerts negative chronotropic effects and protects neonatal rat cardiomyocytes against Ca(2+)-overload with EC(50) ≈ 1-2 nM. Structure-activity studies revealed that a cis-Δ(11,12)- or Δ(14,15)-olefin and a 17(R),18(S)-epoxide are minimal structural elements for antiarrhythmic activity whereas antagonist activity was often associated with the combination of a Δ(14,15)-olefin and a 17(S),18(R)-epoxide. Compared with natural material, the agonist and antagonist analogues are chemically and metabolically more robust and several show promise as templates for future development of clinical candidates. |
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Authors:
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John R Falck; Gerd Wallukat; Narender Puli; Mohan Goli; Cosima Arnold; Anne Konkel; Michael Rothe; Robert Fischer; Dominik N Müller; Wolf-Hagen Schunck |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-06-01 |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 54 ISSN: 1520-4804 ISO Abbreviation: J. Med. Chem. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-06-16 Completed Date: 2011-09-16 Revised Date: 2013-05-24 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: United States |
Other Details:
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Languages: eng Pagination: 4109-18 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, University of Texas Southwestern, Dallas, Texas 75390, United States. j.falck@utsouthwestern.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alkenes
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chemical synthesis*,
pharmacology Animals Animals, Newborn Anti-Arrhythmia Agents / chemical synthesis*, pharmacology Arachidonic Acids / chemical synthesis*, pharmacology Binding Sites Calcium / metabolism Cells, Cultured Eicosapentaenoic Acid / analogs & derivatives*, chemical synthesis*, pharmacology Myocardial Contraction / drug effects* Myocytes, Cardiac / drug effects*, physiology Rats Rats, Wistar Receptors, Eicosanoid / agonists, antagonists & inhibitors Stereoisomerism Structure-Activity Relationship |
| Grant Support | |
ID/Acronym/Agency:
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DK38226/DK/NIDDK NIH HHS; GM31278/GM/NIGMS NIH HHS; P01 DK038226-25/DK/NIDDK NIH HHS; R01 GM031278/GM/NIGMS NIH HHS; R01 GM031278-27/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Alkenes; 0/Anti-Arrhythmia Agents; 0/Arachidonic Acids; 0/Receptors, Eicosanoid; 131339-23-6/17,18-epoxy-5,8,11,14-eicosatetraenoic acid; 1553-41-9/Eicosapentaenoic Acid; 7440-70-2/Calcium |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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