ischemia-reperfusion

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.

Montelukast sodium (MK0476) is an orally available leukotriene receptor antagonist which is widely used for the prophylaxis and chronic treatment of asthma and has been linked to rare cases of clinically apparent liver injury.

MEG hemisulfate (Mercaptoethylguanidine hemisulfate) acts as a highly potent and selective suppressor of inducible NO synthase (iNOS), demonstrating EC50 values of 11.5 μM for iNOS, 110 μM for ecNOS, and 60 μM for bNOS in tissue homogenates. It is notably effective as a peroxynitrite scavenger and blocks peroxynitrite-triggered oxidative mechanisms. Furthermore, this compound offers protective benefits across various experimental inflammation prototypes, such as ischemia/reperfusion injury, hemorrhagic shock, periodontitis, inflammatory bowel disease, and both endotoxic and septic shock.

FK-330 (FR-260330) is a novel orally active inducible nitric oxide synthase inhibitor with potential anticancer and antitumor activity that prevents ischemia and reperfusion injury in rat liver transplantation.

FK-330 dihydrate（FR-260330 dihydrate） is a novel orally active inducible nitric oxide synthase inhibitor with potential anticancer and antitumor activity to prevent ischemia and reperfusion injury in rat liver transplantation.

Raxofelast (IRFI-016) is a hydrophilic, non-systemic, vitamin-like antioxidant that reduces ischemia-reperfusion injury in testis. Raxofelast is a good candidate compound for stopping oxidative stress after acute testicular torsion. Raxofelast has the potential to treat diabetic complications and atherosclerosis.

Tirilazad mesylate (U 74006F) is a non-glucocorticoid, lipid peroxidation inhibitor with antiviral activity and neuroprotective activity.Tirilazad mesylate confines intracellular intramembranous foci, attenuates spinal cord injury induced by trauma, stroke, and ischemia/reperfusion injuries, inhibits toxins in dogs, reduces the effects of Tirilazad mesylate is used in the study of neurological disorders.

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.

DMX-5804 is a potent, selective MAP4K4 inhibitor, with an IC50 of 3 nM.DMX-5804 enhances cardiomyocyte survival, and reduces ischemia-reperfusion injury in mice.

Montelukast (Singular) is an orally available leukotriene receptor antagonist which is widely used for the prophylaxis and chronic treatment of asthma and has been linked to rare cases of clinically apparent liver 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

Luteolinidin chloride is a natural product. It is a potent CD38 inhibitor which can protect the heart against I/R injury with preservation of eNOS function and prevention of endothelial dysfunction in vivo.

Dihydrocapsaicin (CCRIS1589) is isolated from Capsicum fruit. Capsaicin is the primary active component of the heat and pain-eliciting lipid soluble fraction of the Capsicum pepper. Like capsaicin, dihydrocapsaicin is an irritant. Capsaicin is found in natural hot pepper extracts along with a number of impurities, including dihydrocapsaicin and several lesser impurities. Separation by HPLC is required in order to obtain pure dihydrocapsaicin. Dihydrocapsaicin represents about 10% of the compound present in commercial preparations purporting to be pure capsaicin, but it has about the same pungency as capsaicin. VR1 (vanilloid receptor 1) is a heat activated calcium ion channel which functions as a part of the normal nociceptive pain pathway. Capsaicin elicits a sensation of burning pain by activation of VR1 on small, non-myelinated polymodal C-type nociceptive nerve fibers. The potency of dihydrocapsaicin at VR1 appears equivalent to capsaicin. Antioxidant. Reduces oxidation of serum lipids. Mutagenic. Dihydrocapsaicin is an activator of VR1.

Ac2-26 acetate is an active N-terminal peptide of annexin A1(AnxA1). Ac2-26 acetate decreases AnxA1 protein expression and inhibits the activation of NF-κB and MAPK pathways in the injured lung tissue. Ac2-26 acetate attenuates ischemia-reperfusion-induced acute lung injury.

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

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.

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].

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

Tricarbonyldichlororuthenium(II) dimer, a pharmacological CO donor, prevents ischemia/reperfusion (I/R)-induced oxidative damage to the gastric mucosa by enhancing gastric blood flow (GBF) and reducing DNA oxidation and systemic inflammatory response.

(±)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).

Torapsel (42-89-glycoprotein; WAY164339), a fusion protein comprising immunoglobulin, is employed in the investigation of ischemia-reperfusion injury prophylaxis.

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.

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

Klotho-derived peptide 1 (KP1) (56-87), a peptide originating from the human Klotho protein, disrupts TGF-β signaling by binding to TGF-β receptor types 1 and 2 (TGFBR1 and TGFBR2; Kds = 1.41 and 14.6 µM, respectively). Preincubation with KP1 at a concentration of 10 µg/ml hinders the TGF-β-induced escalation of fibronectin and α-smooth muscle actin (α-SMA) levels in NRK-49F rat fibroblasts. Furthermore, in vivo studies reveal that KP1, administered at 1 mg/kg per day, preferentially accumulates in damaged kidneys, leading to significant reductions in serum creatinine and blood urea nitrogen levels, indicators of improved kidney function. Additionally, it decreases kidney fibrosis in mouse models of unilateral ureteral obstruction (UUO) and unilateral ischemia-reperfusion injury-induced renal fibrosis.

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].

Phoenixin-14 TFA (PNX-14) is a blood-brain barrier (BBB)-penetrable neuropeptide with anxiolytic, cardioprotective, and neuroprotective properties. It modulates pituitary gonadotrophin release by enhancing gonadotropin-releasing hormone (GnRH) receptor mRNA expression and promotes insulin secretion. Additionally, PNX-14 TFA offers protection against ischemia/reperfusion (IR) injury in mice and combats oxidative stress by diminishing reactive oxygen species (ROS) and elevating glutathione (GSH) levels [1] [2] [3].

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.

Ac2-26 TFA is an active n-terminal peptide in annexin A1 (AnxA1), which can alleviate acute lung injury caused by ischemia-reperfusion.

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].

Phoenixin-14 (PNX-14), an active endogenous isoform, induces an anxiolytic effect by activating the AHA GnRH system in mice and protects against ischemia/reperfusion-induced cytotoxicity in microglia [1] [2].

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.

Mitochondrial fusion promoter M1, a modulator of mitochondrial dynamics, enhances mitochondrial function and cellular respiration, and has shown efficacy in reducing brain and cardiac damage in rats suffering from cardiac ischemia/reperfusion injury.

SRS16-86 is a novel third-generation ferrostatin, is an inhibitor of ferroptosis.

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.

C3a Receptor Agonist (C3a receptor agonist 1) binds the G protein-coupled C3a receptors (C3aRs) in the immune system complement pathway. Activation of C3aR prevents neutrophils from being mobilized in a model of intestinal ischemia-reperfusion injury. C3aRs are expressed on neural progenitor cells and immature neurons in adult mice. C3a stimulates differentiation of neural progenitor cells in vitro.

Tirilazad, a nonglucocorticoid 21-aminosteroid, serves to inhibit lipid peroxidation. It mitigates the effects of trauma-induced brain or spinal cord injury, as well as damage resulting from stroke, ischemia, and reperfusion injury. Additionally, Tirilazad exhibits antiviral properties against nCoV and offers neuroprotection in cases of ischemic stroke. It is also utilized in subarachnoid hemorrhage research [1] [2] [3].

Ac2-26 TFA, the active N-terminal peptide of Annexin A1 (AnxA1), mitigates ischemia-reperfusion-induced acute lung injury, reduces AnxA1 protein expression, and inhibits the activation of NF-κB and MAPK pathways in affected lung tissue [1].

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

Emodin-8-glucoside (Anthraglycoside B) functions to protect from focal cerebral injury induced by ischemia and reperfusion. Emodin-8-beta-D-glucoside directly stimulates cell proliferation and differentiation of osteoblasts.

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.

FR 167653 sulfate, an orally active and selective inhibitor of p38 MAPK, is effective in treating inflammation, trauma, and ischemia-reperfusion injury in vivo. It acts as a potent suppressor of TNF-α and IL-1β production through specific inhibition of p38 MAPK activity.

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)

CDDO-3P-Im is an orally active inhibitor of necroptosis with chemopreventive effects. CDDO-3P-Im can be used in studies about ischemia/reperfusion.

Sivelestat (ONO5046) is a potent and selective inhibitor of neutrophil elastase with IC50 of 44 nM.

Tat-Gap 19, a peptide inhibitor of connexin43 (Cx43) hemichannels, is derived from the HIV-1 Tat protein transduction domain fused with a nine-amino acid sequence from Cx43 residues 128-136. This compound, at a concentration of 10 µM, effectively suppresses glutamate-induced ATP release in primary rat hepatocytes, indicating inhibition of Cx43 hemichannel activity. Furthermore, Tat-Gap 19 demonstrates therapeutic potential by significantly reducing infarct volume in a mouse cerebral ischemia-reperfusion injury model following middle cerebral artery occlusion (MCAO) at a dosage of 25 mg/kg. Moreover, its intraperitoneal administration at 1 mg/kg per day ameliorates fibrosis and decreases the area of hepatic stellate cells, the precursors to myofibroblasts, expressing α-smooth muscle actin (α-SMA), in a model of thioacetamide-induced liver damage. Additionally, it enhances superoxide dismutase (SOD) activity in hepatic cells from the treated mice, indicating its antioxidative benefits.

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.