title: 17(R),18(S)-epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: structure-activity relationships and stable analogues.
abstract: 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.
authors: Department of Biochemistry, University of Texas Southwestern, Dallas, Texas 75390, United States. j.falck@utsouthwestern.edu
authors: John R
authors: JR
authors: Falck
authors: Gerd
authors: G
authors: Wallukat
authors: Narender
authors: N
authors: Puli
authors: Mohan
authors: M
authors: Goli
authors: Cosima
authors: C
authors: Arnold
authors: Anne
authors: A
authors: Konkel
authors: Michael
authors: M
authors: Rothe
authors: Robert
authors: R
authors: Fischer
authors: Dominik N
authors: DN
authors: Müller
authors: Wolf-Hagen
authors: WH
authors: Schunck
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