infarct

SCH79797 dihydrochloride is an effective and selective antagonist of protease activated receptor 1 (PAR1) with an IC50 of 70 nM and a Ki of 35 nM. SCH79797 dihydrochloride has antiproliferative and pro-apoptotic effects.

Dapansutrile is a potent, selective and orally active NLRP3 inflammasome inhibitor, with Anti-inflammatory and analgesic activity.

Annaosanchun (YC-6) is potentially for the treatment of acute ischemic stroke (AIS).

P7C3-A20, a derivative of P7C3, exhibits both proneurogenic and neuroprotective activities (brackets).

Astragaloside IV (AS-IV), an active component isolated from Astragalus membranaceus, suppresses the activation of ERK1/2 and JNK, and downregulates matrix metalloproteases (MMP)-2, (MMP)-9 in MDA-MB-231 breast cancer cells. Astragaloside IV is a bioactive saponin first isolated from the dried plant roots of the genus Astragalus, which is used in traditional Chinese medicine.1 It dose-dependently inhibits human adenovirus type 3 (HAdV-3) in A549 cells (IC50 = 23 μM; LC50 = 865 μM).It inhibits replication of HAdV-3 and decreases HAdV-3-induced apoptosis. It has diverse protective effects for the cardiovascular, immune, digestive, and nervous systems. In particular, it reduces myocardial infarct size in dogs when administered prior to coronary ligation and reduces reperfusion arrhythmias in isolated rat hearts.

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.

Pinokalant (LOE-908) is a novel non-selective cation channel inhibitor.Pinokalant significantly reduces cortical infarct volume in in vivo experiments, improves the metabolic and electrophysiological status of the ischemic penumbra region, and reduces the size of the lesion on magnetic resonance images in the acute phase after middle cerebral artery occlusion in rats.Pinokalant is a potential SARS-CoV-2 protease inhibitor for the study of stroke.

Cinepazide maleate (MD-67350), a maleate salt form of cinepazide, is a vasodilator.

Pyrithioxin (Encefabol) is a neurodynamic compound, combined with a short period of hyperventilation (HV) was applied in cerebral infarct patients with Hemiplegia. Pyrithioxin is regarded as an encephalotropic or nootropic compound and is reported to act mainly by producing decisive improvements in cerebral metabolism.

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.

L-NIO dihydrochloride, a potent and non-selective NADPH-dependent nitric oxide synthase (NOS) inhibitor, consistently induces focal ischemic infarct in rats. It exhibits inhibitory constants (Kis) of 1.7, 3.9, and 3.9 μM for neuronal (nNOS), endothelial (eNOS), and inducible (iNOS) forms, respectively.

(9R)-RO7185876 (Compound example 16) is a γ-secretase inhibitor. It reduces the secretion of Αβ42. This compound can be employed in the research of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, multi-infarct dementia, senile dementia, or Down syndrome.

Neuroprotective agent 7 (Compound 13) is a brain-penetrant neuroprotective agent that significantly reduces the infarct area in MCAO rat models. It serves as a potent neuroprotective compound and is applicable for studies related to cerebral ischemia and similar conditions.

GluN2B-NMDAR antagonist-2 (compound S-58) is an effective and selective NMDAR-GluN2B antagonist that can cross the blood-brain barrier, with an IC50 value of 74.01 nM. It exhibits mild cytotoxicity and reduces both infarct size and neurological deficit scores in the brain, indicating its potential for stroke research.

Neuroprotective agent 11 (Compound 1a) is an orally active polyphenolic compound that offers significant protection against cerebral ischemia. Its primary activities include inhibiting neuronal inflammation and apoptosis, reducing cerebral infarct size, and improving behavioral symptoms in mice with cerebral ischemia. The mechanism involves downregulating inflammatory factors (iNOS, COX-2) and apoptotic proteins (cleaved-Caspase3, p53). Neuroprotective agent 11 is applicable for research in ischemia-related brain diseases, such as ischemic stroke.

RIPK1-IN-33 is an orally active RIPK1 inhibitor with excellent blood-brain barrier permeability, exhibiting an IC50 of 0.115 μM. It demonstrates significant anti-ferroptosis activity, radical scavenging capability (IC50= 123.3 μM), and anti-lipid peroxidation effects (IC50= 9.72 μM). In transient middle cerebral artery occlusion (tMCAO) models, it significantly reduces cerebral infarct volume and improves neurological scores. RIPK1-IN-33 is suitable for ischemic stroke research.

GSNOR-IN-1 is a prodrug of GSNOR-IN-2 and functions as an S-nitrosoglutathione reductase (GSNOR) inhibitor capable of crossing the blood-brain barrier. GSNOR-IN-1 offers significant protective effects against damage induced by oxygen-glucose deprivation/reoxygenation (OGD/R). It regulates calcium signaling and synaptic function through Clstn1 S-nitrosylation and inhibits neuronal apoptosis. Additionally, GSNOR-IN-1 markedly reduces infarct volume in rat models of ischemic stroke while enhancing neurological function. With its neuroprotective properties, GSNOR-IN-1 holds potential for ischemic stroke research.

(±)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).

N-Methyl-D-aspartate (NMDA) receptors are Ca2+ permeable ligand-gated channels of the central nervous system that are activated after binding of the co-agonists glutamate and glycine. CAY10608 is a propanolamine that potently, selectively, and non-competitively antagonizes the NR2B subunit of NMDA receptors (IC50 = 50 nM). It does not inhibit NR1, NR2A, NR2C, and NR2D subunits and has no significant effects on α-amino-3-hydroxy-5-methyl-4-isoxazolepropioinic acid (AMPA) or kainate receptors. CAY10608 is neuroprotective, since it prevents NMDA-triggered release of lactate dehydrogenase from cultured cortical neurons. Also, CAY10608, when administered intraperitoneally, reduces brain infarct volume resulting from transient ischemia via carotid artery occlusion.

1. Nicotiflorin (Kaempferol-3-O-Rutinoside) has potential therapeutic effects on cerebral ischemic illness. 2. Nicotiflorin has protective effects on reducing memory dysfunction, energy metabolism failure and oxidative stress in multi-infarct dementia model rats.

Moexipril-d5 intended for use as an internal standard for the quantification of moexipril by GC- or LC-MS. Moexipril is a prodrug form of the angiotensin converting enzyme (ACE) inhibitor moexiprilat. It is converted to moexiprilat in vivo by side chain ester hydrolysis. Moexipril inhibits ACE in a cell-free assay (IC50 = 2.7 µM for the rabbit enzyme). It also inhibits phosphodiesterase 4 (IC50s = 38, 160, and 230 µM for PDE4B2, PDE4A5 and PDE4D5, respectively). Moexipril (0.1-30 mg/kg per day) reduces blood pressure in spontaneously hypertensive rats.1 It also reduces infarct volume in a rat model of focal cerebral ischemia when used at a concentration of 0.01 mg/kg.

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.

PI3K/Akt/CREB activator 1 (AE-18) is a selective inducible nitric oxide synthase (iNOS) inhibitor that crosses the blood-brain barrier, reduces infarct size and restores blood supply deficits after ischemia-reperfusion in rats, and is used in studies of vascular dementia and Parkinson's disease.

MRS4719, a potent P2X4 receptor antagonist, exhibits a half-maximal inhibitory concentration (IC50) of 0.503 μM for the human P2X4 receptor. Demonstrating both neuroprotective and neuro-rehabilitative effects, it can decrease infarct volume and brain atrophy in an ischemic stroke model. Additionally, MRS4719 mitigates ATP-induced calcium influx in primary human monocyte-derived macrophages, making it a valuable tool for researching ischemic stroke.