CAY10665

Isolated neonatal rat cardiomyocytes, which spontaneously beat in culture, are used to evaluate the antiarrhythmic effects of polyunsaturated fatty acids (PUFA).¹ In this model, the ω-3 PUFA eicosapentaenoic acid (EPA, 3-10 μM) reduces the contraction rate of cells, indicating a positive antiarrhythmic effect.¹ Cytochrome P450 metabolites of EPA are more potent, with 17,18-epoxyeicosatetraenoic acid (17,18-EET) reducing contractions at 30 nM.² CAY10665 is a bioisostere of 17,18-EET which is approximately 50% more effective at reducing arrhythmic contraction frequency, without affecting amplitude, when tested at 30 nM.³ This disubstituted oxamide represents a stable analog of 17,18-EET which may be used to study the mechanism of regulation of cardiomyocyte contractility by EPA metabolites.

WARNING This product is not for human or veterinary use.

1. Kang, J.X., and Leaf, A. Effects of long-chain polyunsaturated fatty acids on the contraction of neonatal rat cardiac myocytes. Proc. Natl. Acad. Sci. USA 91(21), 9886-9890 (1994).

2. Arnold, C., Markovic, M., Blossey, K., et al. Arachidonic acid-metabolizing cytochrome P450 enzymes are targets of omega-3 fatty acids. The Journal of Biological Chemisty 285(43), 32720-32733 (2010).

3. Falck, J.R., Wallukat, G., Puli, N., et al. 17(R),18(S)-Epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: Structure-activity relationships and stable analogues. J. Med. Chem. 54(12), 4109-4118 (2011).