HMR 1556 is a chromanol derivative and is an IKs blocker (IC50s of 10.5 nM and 34 nM in canine and guinea pig left ventricular myocytes, respectively).
Broad spectrum MMP inhibitor (IC50< sub> values are 0.7, 0.9, 13, 16 and 1170 nM for MMP-2, MMP-13, MMP-9, MMP-3 and MMP-1 respectively). Attenuates early left ventricular dilation after experimental myocardial infarction in mice.
Pyrromecaine is a local anesthetic used for surface anesthesia. Pyromecaine has a wide spectrum of antiarrhythmic action, exerts a favorable effect on the contractility of the left ventricle, and on the myocardial blood flow following the ligation of the
PD 122860 is a dihydropyridine with calcium channel blocking and sodium channel stimulating properties. In the rat heart, PD 122860 increased left ventricular contractility, decreased coronary resistance and altered the shape of the electrocardiogram T-wa
(±)14(15)-EET is a metabolite of arachidonic acid that is formed via epoxidation of arachidonic acid by cytochrome P450.[1],[2] It prevents increases in leukotriene B4, ICAM-1, and chemokine (C-C motif) ligand 1 (CCL2) induced by oxidized LDL in primary rat pulmonary artery endothelial cells (RPAECs) when used at a concentration of 1 μM.[3] (±)14(15)-EET induces dilation of preconstricted isolated canine coronary arterioles (EC50 = 0.2 pM).[4] It reduces myocardial infarct size as a percentage of the area at risk in a canine model of ischemia-reperfusion injury induced by left anterior descending coronary artery (LAD) occlusion when administered at a dose of 0.128 mg kg prior to occlusion or reperfusion.[5] Reference:[1]. Chacos, N., Falck, J.R., Wixtrom, C., et al. Novel epoxides formed during the liver cytochrome P-450 oxidation of arachidonic acid. Biochem. Biophys. Res. Commun. 104(3), 916-922 (1982).[2]. Oliw, E.H., Guengerich, F.P., and Oates, J.A. Oxygenation of arachidonic acid by hepatic monooxygenases. Isolation and metabolism of four epoxide intermediates. J. Biol. Chem. 257(7), 3771-3781 (1982).[3]. Jiang, J.-X., Zhang, S.-J., Xiong, Y.-K., et al. EETs attenuate ox-LDL-induced LTB4 production and activity by inhibiting p38 MAPK phosphorylation and 5-LO BLT1 receptor expression in rat pulmonary arterial endothelial cells. PLoS One 10(6), e0128278 (2015).[4]. Oltman, C.L., Weintraub, N.L., VanRollins, M., et al. Epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids are potent vasodilators in the canine coronary microcirculation. Circ. Res. 83(9), 932-939 (1998).[5]. Nithipatikom, K., Moore, J.M., Isbell, M.A., et al. Epoxyeicosatrienoic acids in cardioprotection: Ischemic versus reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 291(2), H537-H542 (2006).
Neuromedin U (NMU) is a neuropeptide first demonstrated to drive smooth muscle contraction.1Translated as a 174 amino acid propeptide, NMU is cleaved to different lengths in different animals. It has diverse receptor-mediated rolesin vivo, as it regulates feeding, vasoconstriction, nociception, and bone remodeling and contributes to obesity, cancer and septic shock.2,2NMU-25 is the active form of NMU in humans. It binds with high affinity to receptors on human left ventricle and coronary artery (KDs = 0.26 and 0.11 nM, respectively), eliciting endothelium-independent vasoconstriction.3NMU-25 also suppresses glucose-stimulated insulin secretion in human islets, and this effect is lost in NMU R165W mutants, resulting in early-onset obesity.4 1.Mitchell, J.D., Maguire, J.J., and Davenport, A.P.Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin SBritish Journal of Pharmacology15887-103(2009) 2.Greenwood, H.C., Bloom, S.R., and Murphy, K.G.Peptides and their potential role in the treatment of diabetes and obesityRev.Diabet.Stud.8(3)355-368(2011) 3.Mitchell, J.D., Maguire, J.J., Kuc, R.E., et al.Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular systemCardiovascular Research81353-361(2009) 4.Alfa, R.W., Park, S., Skelly, K.R., et al.Suppression of insulin production and secretion by a decretin hormoneCell Metabolism21(2)323-333(2015)
1-O-Hexadecyl-sn-glycerol is a bioactive alkyl glyceryl ether. It reduces UVB-induced cell death and production of reactive oxygen species (ROS) and prostaglandin E2 in normal human epidermal keratinocytes (NHEKs). 1-O-Hexadecyl-sn-glycerol (50 μM) increases coronary flow and left ventricular developed pressure and reduces malondialdehyde (MDA) formation ex vivo in a rat heart model of ischemia reperfusion injury. [2].Maulik, N., Tosaki, A., Engelman, R.M., et al. Myocardial salvage by chimyl alcohol: Possible role of peroxisomal dysfunction in reperfusion injury Ann. N.Y. Acad. Sci. 723(1), 380-384 (1994).
Tyr-α-CGRP is an N-terminal extended tyrosinated analogue of α-calcitonin gene-related peptide . It binds to amylin receptors AMY1 and AMY3 in COS-7 cells expressing the human receptors (IC50s = 141 and 1.86 nM, respectively). Tyr-α-CGRP also binds to and stimulates cAMP accumulation in rat L6 myocytes (IC50 = 4 nM; EC50 = 12 nM). It also binds to rat brain and spleen membrane preparations (IC50s = 0.2 and 0.5 nM, respectively), induces positive chronotropic and inotropic effects in isolated right and left guinea pig atria (EC50s = 282 and 74 nM, respectively), and inhibits the twitch response in rat vas deferens (EC50 = 1.9 nM).
Ruboxistaurin is a PKC beta inhibitor. Ruboxistaurin reduces oxidative stress and attenuates left ventricular hypertrophy and dysfunction in rats with streptozotocin-induced diabetes. Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-β1
Ruboxistaurin mesylate monohydrate is a PKC beta inhibitor potentially for the treatment of diabetic nephropathy and diabetic macular edema. Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-β1 Smad and GRAP pathways. Ruboxistaurin reduces oxidative stress and attenuates left ventricular hypertrophy and dysfunction in rats with streptozotocin-induced diabetes. Ruboxistaurin inhibits retinal neovascularization via suppression of phosphorylation of ERK1 2 and Akt.