myocardial ischemia

NLRP3-IN-2 (5-Chloro-N-(p-sulfamoylphenethyl)-o-anisamide), an intermediate capable of synthesizing glibenclamide, exerts an inhibitory effect on the formation of NLRP3 inflammatory vesicles in cardiomyocytes, limiting infarct size after myocardial ischemia/reperfusion in mice and has no effect on metabolism.

Sinitrodil (ITF-296) is a guanylate cyclase stimulant that may be used in the treatment of myocardial ischemia and angina pectoris.

Diaminohydroxypropanetetraacetic acid has been investigated for the treatment of Vascular Disease, Coronary Disease, Myocardial Ischemia, Coronary Restenosis, and Coronary Artery Disease, among others

BIIB 722 Mesylate is a selective sodium-hydrogen exchange inhibitor with cardioprotective properties and can be used to study myocardial ischemia and myocardial infarction.

Protectin D1 (Neuroprotectin D1) is a neuroprotectin produced by neuronal cells and is a potential cardioprotective agent.Protectin D1 attenuates myocardial ischemia/reperfusion injury and inhibits imiquimod-induced psoriasis-like skin inflammation by modulating the PI3K/AKT signaling pathway.

SSR69071 is a potent, orally active, and selective inhibitor of neutrophil elastase. SSR69071 displays a higher affinity for human elastase (Ki =0.0168 nM) than for rat (Ki =3 nM), mouse (Ki =1.8 nM), and rabbit (Ki = 58 nM) elastases [2]. SSR69071 reduces myocardial infarct size following ischemia-reperfusion injury [1]. SSR69071 also has the potential for the treatment of chronic obstructive pulmonary diseases, asthma, emphysema, cystic fibrosis, and several inflammatory diseases.

LUF6096 (CF-602) is a potent allosteric enhancer of the adenosine A3 receptor, exhibiting the capability to enhance agonist binding allosterically while demonstrating low orthosteric affinity across adenosine receptors. It displays protective effects in myocardial ischemia/reperfusion injury.

Licochalcone D may be a potential drug for human melanoma treatment by inhibiting proliferation, inducing apoptosis via the mitochondrial pathway and blocking cell migration and invasion. Licochalcone D has cardioprotective potential against myocardial is

Ranolazine (RS 43285-003) is a calcium uptake inhibitor via the sodium/calcium channel, used to treat chronic angina. It affects the sodium-dependent calcium channels during myocardial ischemia in rabbits by altering the intracellular sodium level.

Minocycline hydrochloride (Minocycline HCl) is a tetracycline antibiotic with excellent absorption and tissue penetration that is used for several bacterial infections as well as treatment of acne. Minocycline hydrochloride can cause both an acute hepatitis-like syndrome occurring within 1 to 3 months of starting therapy or a more insidious chronic hepatitis with autoimmune features typically after long-term treatment.

Cipepofol (HSK3486) is a GABAA receptor agonist with sedative properties and protective effects in a variety of cardiovascular diseases.Cipepofol activates the Sirtuin1 (Sirt1)/Nrf2 pathway and induces apoptosis in cardiomyocytes, and can be used to study myocardial infarction, myocardial ischemia/reperfusion injury, and octopus pot syndrome.

20(R)-Notoginsenoside R2 is a natural product with Promote blood circulation and improve myocardial ischemia

1. Ilexsaponin A (Ilexsaponin A1) shows protective effects on ischemia-reperfusion-induced myocardial injury through anti-apoptotic pathway.

Aralosides possess protective effect against experimental myocardial ischemia and infarction, the mechanism of myocardial protection may be attributed to the amelioration of FFA metabolic deterioration and membrane peroxidation induced by oxygen free radi

Echinatin exerts a protective effect against ischemia/reperfusion (I/R)-induced myocardial injury on hearts, this effect may be attributed to the antioxidant and anti-inflammatory activities of this compound. Echinatin can inhibit DNP-ATPase activity whil

Nangibotide, a TREM-1 receptor inhibitor, modulates the innate immune response and has demonstrated the potential to reduce systemic and localized inflammatory reactions in rodent models of myocardial ischemia-reperfusion [1].

(±)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).

Baohuoside aglycone possesses cardioprotective effect in prevention of ischemia/ reperfusion injury and reduce the myocardial infraction, the mechnism is due to the reduction of the injury of free radicals. Baohuoside VII in vivo exhibits significant anti

Ru360, an oxygen-bridged dinuclear ruthenium amine complex, is a selective mitochondrial calcium uptake inhibitor. Ru360 potently inhibits Ca2+ uptake into mitochondria with an IC50 of 0.184 nM. Ru360 binds to mitochondria with high affinity (Kd of 0.34 nM). Ru360 has antiarrhythmic and cardioprotective effects[1][2]. Ru360 permeates slowly into the cell, and specifically inhibits mitochondrial calcium uptake in intact cardiomyocytes and in isolated heart. 1 μm Ru360 is taken up by myocardial cells and accumulated in the cytosol in a biphasic manner[1]. During pelleting hypoxia, Ru360 (10 µM) significantly improves cell viability in wild type cardiomyocytes[3]. Ru360 (15-50 nmol/kg) treatment abolishes the incidence of arrhythmias and haemodynamic dysfunction elicited by reperfusion in a whole rat model. Ru360 administration partially inhibits calcium uptake, preventing mitochondria from depolarization by the opening of the mitochondrial permeability transition pore (mPTP)[1]. [1]. G de J García-Rivas, et al. Ru360, a Specific Mitochondrial Calcium Uptake Inhibitor, Improves Cardiac Post-Ischaemic Functional Recovery in Rats in Vivo. Br J Pharmacol. 2006 Dec;149(7):829-37. [2]. M A Matlib, et al. Oxygen-bridged Dinuclear Ruthenium Amine Complex Specifically Inhibits Ca2+ Uptake Into Mitochondria in Vitro and in Situ in Single Cardiac Myocytes. J Biol Chem. 1998 Apr 24;273(17):10223-31. [3]. Lukas J Motloch, et al. UCP2 Modulates Cardioprotective Effects of Ru360 in Isolated Cardiomyocytes During Ischemia. Pharmaceuticals (Basel). 2015 Aug 4;8(3):474-82.

TRPC1/6 and Piezo2 inhibitor. Exhibits same effect as L-enantiomer, GsMTx4 (Cat. No. 4912) on TRPC channels. Inhibits mechanosensitive currents by ~70%. Protects against myocardial infarction in mouse ischemia/reperfusion model. Resistant to proteolytic digestion.

Nangibotide TFA, a TREM-1 receptor inhibitor, modulates the innate immune response and attenuates both systemic and localized inflammatory reactions in rodent models of myocardial ischemia-reperfusion [1].

Bisoprolol is a cardioselective β1-adrenergic blocker used for secondary prevention of heart failure, myocardial, angina pectorisinfarction (MI) and mild to moderate hypertension.

Anti-MI/R injury agent 1 (compound 18), derived from Panaxatriol, represents an orally administered, potent agent against myocardial ischemia/reperfusion (MI/R) injury. It improves cell viability in cardiomyocytes subjected to oxygen-glucose deprivation and reperfusion (OGD/R)-induced injury. Furthermore, this compound significantly reduces myocardial infarction size, diminishes levels of circulating cardiac troponin I (cTnI), and mitigates cardiac tissue damage in rat models [1].

ROS-IN-2 (compound 85), a seco-lupane triterpenoid derivative, inhibits reactive oxygen species (ROS) production and shields mitochondria from oxidative damage by curtailing the generation of oxidative stressors. It has applications in myocardial ischemia/reperfusion (MI/R) injury research [1].

INF200 (compound 5), a sulfonylurea-based inhibitor of NLRP3 and associated pyroptosis, exhibits cardiometabolic benefits in a rat model of high-fat diet (HFD)-induced metaflammation and demonstrates anti-inflammatory effects by reducing IL-1β release in human macrophages at a concentration of 10 μM. Additionally, it enhances glucose and lipid profiles, diminishes systemic inflammation and cardiac dysfunction biomarkers, notably BNP, and ameliorates myocardial damage linked to ischemia/reperfusion injury (IRI) as assessed by hemodynamic parameters [1].

PD-166793 is an orally active, potent and selective MMP inhibitor with inhibitory effects on MMP-2, MMP-3 and MMP-13.PD-166793 ameliorates myocardial ischemia and reperfusion injury in a rat model of heart failure.PD-166793 is an orally active, potent and selective MMP inhibitor with inhibitory effects on MMP-2, MMP-3, and MMP-13.

MitoA is a ratiometric mass spectrometry probe that can be used for assessing changes in H2S within mitochondria in vivo. MitoA contains a triphenylphosphonium cation component that drives its accumulation in mitochondria where its aryl azide moiety selectively reacts with H2S to produce an amine product, MitoN. Quantifying the MitoN/MitoA ratio by LC-MS/MS reflects the mitochondrial matrix H2S concentration. In a mouse model of acute myocardial infarction with MitoA administered prior to ischemia, the MitoN/MitoA ratio is increased only in the region of ischemia.

Taprostene (CG-4203), a synthetic and chemically stable analogue of Prostacyclin (PGI2), effectively protects the endothelium and myocardium following acute myocardial ischemia and reperfusion in cats. It enhances cytoprotective actions and minimizes undesired hemodynamic effects [1].

KR-32568 is a sodium/hydrogen exchanger 1 (NHE-1) inhibitor (IC50: 230 nM). KR-32568 exhibits potent cardioprotective effects. When used at a concentration of 10 μM, it restored cardiac systolic function in an isolated ischemic rat heart model. KR-32568 (0.3 mg/kg) reduced the size of myocardial infarction in a rat model of ischemia and reperfusion injury.

Deltorphin II is a peptide agonist of δ2-opioid receptors.1,2It is selective for δ-opioid receptors over μ- and κ-opioid receptors in radioligand bindings assays (Kis = 0.0033, >1, and >1 μM, respectively) and induces [35S]GTPγS binding in mouse brain membrane preparations (EC50= 0.034 μM). Deltorphin II (0.12 mg/kg) decreases the infarction zone:risk zone ratio in a rat model of myocardial ischemia-reperfusion injury induced by coronary occlusion, an effect that can be reversed by the δ2-opioid receptor antagonist naltriben but not the δ1-opioid receptor antagonist BNTX.3Intrathecal administration of deltorphin II (15 μg/animal) increases latency to withdraw in the paw pressure and tail-flick tests in rats.4 1.Raynor, K., Kong, H., Chen, Y., et al.Pharmacological characterization of the cloned κ-, δ-, and μ-opioid receptorsMol. Pharm.45(2)330-334(1994) 2.Scherrer, G., Befort, K., Contet, C., et al.The delta agonists DPDPE and deltorphin II recruit predominantly mu receptors to produce thermal analgesia: A parallel study of mu, delta and combinatorial opioid receptor knockout miceEur. J. Neurosci.19(8)2239-2248(2004) 3.Maslov, L.N., Barzakh, E.I., Krylatov, A.V., et al.Opioid peptide deltorphin II simulates the cardioprotective effect of ischemic preconditioning: role of δ2-opioid receptors, protein kinase C, and KATP channelsBull. Exp. Biol. Med.149(5)591-593(2010) 4.Labuz, D., Toth, G., Machelska, H., et al.Antinociceptive effects of isoleucine derivatives of deltorphin I and deltorphin II in rat spinal cord: A search for selectivity of delta receptor subtypesNeuropeptides32(6)511-517(1998)

D-GsMTx4 TFA, a selective spider venom peptide, is a TRPC1/6 and Piezo2 inhibitor that inhibits cation-permeable mechanosensitive channels (MSCs) belonging to the Piezo and TRP channel families, blocks cation-selective stretch-activated channels (SACs), and attenuates lysophosphatidylcholine (LPC)-induced astrocyte toxicity and microglia reactivity. toxicity and microglia reactivity.D-GsMTx4 TFA prevented myocardial infarction in a mouse model of ischemia/reperfusion and can be used to characterize the role of excitatory MSCs in normal physiology and pathology.

Regaloside C is a glycerol glucoside isolated from Lilium genus with anti-inflammatory properties.

Pseudoginsenoside F11 (Ginsenoside A1) is a component of Panax quinquefolium (American ginseng) which main pharmacological activities are positive inotropic effect on isolated heart function, good therapeutic effect on myocardial ischemia, and good protective effect on cardio-cerebrovascular system and nervous system.

TJ-M2010-5 is a MyD88 inhibitor that binds to the TIR domain to interfere with its homodimerization and suppress MyD88 signaling. TJ-M2010-5 can be used in myocardial ischemia/reperfusion injury studies.

Pexelizumab (h5G1.1-SC), a humanized scFv monoclonal antibody, targets the C5 complement component, thereby inhibiting apoptosis and leukocyte infiltration. It is utilized in researching cerebral ischemia-reperfusion (IR) injury and myocardial infarction [1] [2].

CVT-2512 is a metabolite of Renolazine, which has anti-myocardial ischemia effect.

Caspase-9 Inhibitor III (Ac-LEHD-cmk), a caspase-9 inhibitor, exhibits protective effects against ischemia-reperfusion-induced myocardial injury.

CVT-2513 is a metabolite of Renolazine, which has anti-myocardial ischemia effect.

LS-102 is a selective inhibitor of the E3 ligase synoviolin (Syvn1), an astragaloside IV derivative, which attenuates myocardial ischemia/reperfusion injury by inhibiting mitochondrial fission.LS-102 inhibits Syvn1 auto-ubiquitylation, which ameliorates amyloidazole-induced slowing of the heart rate, and is useful for studying cardiovascular diseases.

Nicorandil-d4 is intended for use as an internal standard for the quantification of nicorandil by GC- or LC-MS. Nicorandil is an activator of sulfonylurea receptor 2B (SUR2B) linked to ATP-sensitive potassium channel Kir6.2 (EC50 = ~10 µM) and a nitric oxide (NO) donor. It is selective for SUR2B/Kir6.2 over the SUR2A/Kir6.2 channel (EC50 = >500 µM). Nicorandil activates soluble guanylate cyclase in a cell-free assay and relaxes partially depolarized isolated bovine coronary artery strips (EC50 = 4.4 µM). It decreases mean blood pressure, coronary resistance, and heart rate, as well as increases coronary sinus outflow, in dogs when administered intravenously at a dose of 1 mg/kg. Nicorandil increases survival and decreases infarct size in a rabbit model of myocardial ischemia-reperfusion injury induced by left coronary artery occlusion. Formulations containing nicorandil have been used in the treatment of angina pectoris.

C18 Ceramide-1-phosphate (d18:1/18:0) is a long-chain molecule identified in murine skin known to promote the migration of mouse bone marrow-derived multipotent stromal cells and human umbilical vein endothelial cells (HUVECs) at concentrations of 0.5 to 5 µM. It exhibits elevated levels in CFPAC-1 pancreatic ductal adenocarcinoma cells compared to pancreatic cancer stem cells, and its myocardial concentration is heightened in Langendorff isolated perfused mouse hearts under an ex vivo ischemia model.

Delcasertib (KAI-9803) hydrochloride, a potent and selective δ-protein kinase C (δPKC) inhibitor, shows promise in reducing ischemia and reperfusion injury in animal models of acute myocardial infarction (MI) [1] [2].

Falipamil is a verapamil derivative and a calcium channel antagonist. Falipamil exerts antitachycardic effects by a direct action on the sinus node. Falipamil decreases HR at exercise in normal subjects and may exert antianginal effects in patients with m

Linsidomine hydrochloride (SIN-1 chloride) is considered as a metabolite of moxidomine, with vasodilation, inhibition of platelet aggregation, and antiangina activity. In myocardial ischemia-reperfusion models, Linsidomine hydrochloride to reduce myocardial necrosis and reperfusion induced endothelial dysfunction is associated with the cavernosal mechanism of action involved in nitric oxide release.

Ned-K is a nicotinic acid adenine dinucleotide phosphate (NAADP) antagonist that exhibits an inhibitory effect on myocardial ischemia and reperfusion (sIR)-induced calcium oscillations.

Bopindolol is a non-selective β-adrenergic receptor antagonist. In vivo, bopindolol decreases heart rate and blood pressure and attenuates ischemia-induced myocardial acidosis in dogs. Formulations containing bopindolol have been used to treat essential and renovascular hypertension.

Barlerin (8-O-Acetylshanzhiside methyl ester) has potential against cerebral ischemic injury, and its protective effect on oxygen-glucose deprivation-induced injury might be due to the suppression of intracellular Ca2+ elevation and caspase-3 activity, and improvement of mitochondrial energy metabolism.8-O-Acetylshanzhiside methylester can increase angiogenesis and improve functional recovery after stroke.8-O-Acetylshanzhiside methylester has protective effects on experimental myocardial ischemia injury, the effects might be due to block of myocardial inflammatory cascades through an HMGB1-dependent NF-κB signaling pathway.8-O-Acetylshanzhiside methylester protects diabetic brain against I/R injury by alleviating diabetic cerebral I/R injury and attenuating blood–brain barrier (BBB) breakdown, and its protective effects may involve HMGB-1 and NF-κB signalling pathway.

TAT-NSF700 Fusion Peptide acetate is a membrane-permeable inhibitor of N-ethyl-maleimide-sensitive factor (NSF), a fusion peptide with potential anti-inflammatory activity.TAT-NSF700 Fusion Peptide acetate interacts with intracellular organelles and can be used to investigate Myocardial ischemia and reperfusion injury.

L-2286 is a novel PARP inhibitor. L-2286 exerted significant protective effect against ischemia-reperfusion-induced myocardial injury in both experimental models. More importantly, L-2286 facilitated the ischemia-reperfusion-induced activation of Akt, extracellular signal-regulated kinase, and p38-MAPK in both isolated hearts and in vivo cardiac injury.

Mexiletine hydrochloride (KOE-1173 hydrochloride) is a voltage-gated sodium channel blocker and a Class IB antiarrhythmic drug. Mexiletine hydrochloride exerts antiarrhythmic effects by inhibiting sodium current in myocardial cells, thereby reducing the rise rate of cardiac action potential (phase 0) and reducing the automaticity of Purkinje fibers.

Nicorandil (SG-75)(Ikorel) acts by relaxing the smooth muscle of the blood vessels, especially those of the venous system. It undertakes this through two methods. Firstly, by activating potassium channels, and secondly by donating nitric oxide to activate the enzyme guanylate cyclase. Guanylate cyclase causes activation of cGMP leading to both arterial and venous vasodilatation by de-phosphorylation of the myosin light chain.