AUH-6-96 is an inhibitor of JAK STAT signaling, inhibiting both constitutive and interleukin-6-induced STAT3 phosphorylation, selectively affecting cell viability only of cancer cells harboring aberrant JAK STAT signaling.
N-Desbutyl dronedarone is an active metabolite of the antiarrhythmic agent dronedarone .1,2,3It is formed from dronedarone by cytochrome P450s (CYPs) and monoamine oxidase (MAO) in human hepatocyte preparations.4N-Desbutyl dronedarone inhibits the binding of 3,3’,5-triiodo-L-thyronine to the thyroid hormone receptors TRα1and TRβ1(IC50s = 59 and 280 μM for the chicken and human receptors, respectively).1It inhibits CYP2J2-mediated formation of 14,15-EET from arachidonic acid and soluble epoxide hydrolase-mediated formation of 14,15-DHET from 14,15-EET (IC50s = 1.59 and 2.73 μM, respectively, in cell-free assays).2N-Desbutyl dronedarone decreases intracellular ATP levels in H9c2 rat cardiomyocytes (IC50= 1.07 μM) and inhibits mitochondrial complex I, also known as NADH dehydrogenase, and mitochondrial complex II, also known as succinate dehydrogenase, activities in isolated rat heart mitochondria (IC50s = 11.94 and 24.54 μM, respectively).3 1.Van Beeren, H.C., Jong, W.M.C., Kaptein, E., et al.Dronerarone acts as a selective inhibitor of 3,5,3’-triiodothyronine binding to thyroid hormone receptor-α1: in vitro and in vivo evidenceEndocrinology144(2)552-558(2003) 2.Karkhanis, A., Tram, N.D.T., and Chan, E.C.Y.Effects of dronedarone, amiodarone and their active metabolites on sequential metabolism of arachidonic acid to epoxyeicosatrienoic and dihydroxyeicosatrienoic acidsBiochem. Pharmacol.146188-198(2017) 3.Karkhanis, A., Leow, J.W.H., Hagen, T., et al.Dronedarone-induced cardiac mitochondrial dysfunction and its mitigation by epoxyeicosatrienoic acidsToxicol. Sci.163(1)79-91(2018) 4.Klieber, S., Arabeyre-Fabre, C., Moliner, P., et al.Identification of metabolic pathways and enzyme systems involved in the in vitro human hepatic metabolism of dronedarone, a potent new oral antiarrhythmic drugPharmacol. Res. Perspec.2(3)e00044(2014)
S-Nitrosothiols (RSNOs) are a class of molecules that function as exogenous and endogenous nitric oxide (NO) donors. RSNOs found in vivo include proteins such as S-nitrosohemoglobin and S-nitrosoalbumin, as well as low molecular weight species such as S-nitrosoglutathione (GSNO) and S-nitrosocysteine (CysNO). CAY10563 is a member of a new class of S-nitrosothiol species that act as an NO donors under acidic conditions. It decomposes with a half-life of one minute in 0.1 M phosphate buffer, pH 5.0, at 37°C and relaxes phenylephrine-constricted rat aortic strips 59% and 16% at pH 6.0 and 7.4, respectively.
S-Nitrosothiols (RSNOs) are a class of molecules that function as exogenous and endogenous nitric oxide (NO) donors. RSNOs found in vivo include proteins such as S-nitrosohemoglobin and S-nitrosoalbumin, as well as low molecular weight species such as S-nitrosoglutathione (GSNO) and S-nitrosocysteine (CysNO). CAY10564 is a member of a new class of S-nitrosothiol species that act as NO donors under acidic conditions. It decomposes with a half-life of one minute in 0.1 M phosphate buffer, pH 5.0, at 37°C and relaxes phenylephrine-constricted rat aortic strips 59% and 16% at pH 6.0 and 7.4, respectively.
19R(20S)-EpDPA is an oxylipin and a metabolite of docosahexaenoic acid .1,2It is formed from DHA by various cytochrome P450 (CYP) isoforms in a stereoselective manner.219R(20S)-EpDPA (30 nM) prevents calcium-induced increases in the spontaneous beating of isolated neonatal rat cardiomyocytes (NRCMs).3 1.Cinelli, M.A., Yang, J., Scharmen, A., et al.Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acidsJ. Lipid Res.59(11)2237-2252(2018) 2.Lucas, D., Goulitquer, S., Marienhagen, J., et al.Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450J. Lipid Res.51(5)1125-1133(2010) 3.Burke, J.E., and Dennis, E.A.Phospholipase A2 structure/function, mechanism, and signalingJ. Lipid Res.50(Suppl)S237-S242(2009)