ischemia-reperfusion injury

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 and neuroprotective activities. It confines intracellular intramembranous foci, attenuates spinal cord injuries induced by trauma, stroke, and ischemia reperfusion injuries, inhibits toxins in dogs, and is used in the study of neurological disorders.

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

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.

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 and effective nitric oxide synthase inhibitor. It can prevent ischemia and reperfusion injury in rat liver transplantation.

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, displaying higher affinity for human elastase (Ki = 0.0168 nM) compared to rat (Ki = 3 nM), mouse (Ki = 1.8 nM), and rabbit (Ki = 58 nM) elastases [2]. It reduces myocardial infarct size following ischemia-reperfusion injury [1] and has potential for treating chronic obstructive pulmonary diseases, asthma, emphysema, cystic fibrosis, and various 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.

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.

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.

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.

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

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.

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

GSK329 is an effective and selective inhibitor of TNNI3 Interacting Kinase (TNNI3K). GSK329 exhibits positive cardioprotective outcomes in the model of ischemia/reperfusion cardiac injury.

NS1619 have cardio-protective effects after ischemia-reperfusion injury.

NS309 is a nonselective activator of small- and intermediate-conductance Ca2+-activated K+ (SK/KCa2 and IK/KCa3.1) channels (EC50s range from 0.12-1.2 µM for SK channels and 10-90 nM for IK channels). It can also activate voltage-gated Kv11.1 channels (hE

TIQ-A is a PARP1 inhibitor which involved in DNA single-strand break repair via the base excision repair pathway. PARP1 is triggered by DNA damage and its excessive activation has been proposed as a causative factor in many pathological conditions includi

BGP-15 (BGP-15 2HCl) is a PARP inhibitor with protecting effect after ischemia-reperfusion injury.

Bucillamine (DE019) protects against Ischemia reperfusion injury in high-risk organ transplants and inhibits the production of VEGF. Bucillamine is an orally active sulfhydryl donor and antioxidant with antirheumatic and antiangiogenic properties. Bucillamine can be used for studies about choroidal neovascularization and rheumatoid arthritis.

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.

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.

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

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.

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

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].

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.

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)

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.

Regaloside C, a glycerol glucoside isolated from the Lilium genus, exhibits notable anti-inflammatory properties.

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].

NecroX-7 (LC-280126) is a potent free radical scavenger and HMGB1 (high-mobility group box 1) inhibitor. It serves as an antidote to acetaminophen toxicity and exerts a protective effect by preventing HMGB1 release in ischemia reperfusion injury. Additionally, NecroX-7 inhibits HMGB1-induced release of TNF and IL-6 and the expression of TLR-4 and receptor for advanced glycation end products. This compound may be used for graft-versus-host disease (GVHD) research [1].

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.

Trametenolic acid is a natural compound extracted from certain fungi that can inhibit the proliferation of tumor cells in vitro and protect the brain against ischemia-reperfusion injury by modulating signaling pathways such as PI3K Akt mTOR.

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

FR 167653 free base is an orally active p38 MAPK inhibitor and is effective in treating inflammation, relieving trauma, and ischemia-reperfusion injury in vivo. It also is a potent suppressor of TNF-α and IL-1β production via specific inhibition of p38 MA

KR-67607, also known as NTX-101 is novel selective 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor. KR-67607 decreased 4-hydroxynonenal expression and increased antioxidant and mucus secretion in BAC-treated rat eyes. KR-67607 showed its protective effects against ischemia-reperfusion-induced eye injury. KR-67607 effectively reduced cortisol levels in mouse eyes and maintained the trabecular meshwork (TM) structure in the presence of transient ischemic stress. Furthermore, KR-67607 reversed the elevation of intra-ocular pressure (IOP), suggesting that the TM structure maintained by KR-67607 prevented the excessive rise in IOP that exacerbates glaucoma.

U-74389G is an antioxidant which prevents iron-dependent lipid peroxidation. It protects against ischemia-reperfusion injury in animal heart, liver, and kidney models.[1],[2],[3],[4]

TRC160334 is a hydroxylase inhibitor of hypoxia-inducible factor (HIF). It is employed in research about ischemia/reperfusion injury.

(±)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).

BI-9627 is a selective and potent sodium hydrogen exchange isomer 1 (NHE1) inhibitor.BI-9627 partially reverses the effects of DMA with IC50 values of 6 and 31 nM in the intracellular pH recovery (pHi) and human platelet lysis assays.BI-9627 is often used as a negative control for BI-0054, which can be used for the study of ischemia-reperfusion injury in isolated hearts. BI-9627 is often used as a negative control for BI-0054 and can be used to study ischemia-reperfusion injury in isolated hearts.

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

Crocin II (Crocetin gentiobiosylglucosyl ester) has anti-inflammatory and anti-apoptotic effects against gastric ischemia-reperfusion injury in rats, the effect of crocin is mainly mediated by reducing the protein expression of iNOS and caspase-3. Crocin II can ameliorate CCl4-induced liver injury via inhibition of inflammatory cytokines, caspase3 and oxidative stress along with modulation of liver metabolizing enzymes favoring elimination of CCl4 toxic metabolite. Crocin II has antihyperlipidemic effect, may be due to the inhibition of pancreatic lipase and crocin, and its metabolite, Crocin II , can improve hyperlipidemia. Crocin has antidepressant effects by increasing CREB, BDNF and VGF levels in hippocampus.

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 (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.