cerebral artery occlusion

CaCCinh-A01 is an inhibitor of the calcium-activated chloride channel (CaCC, 10 μM) and TMEM16A (IC50: 2.1 μM).

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.

Piclozotan (anhydrous), a 5-HT1A receptor agonist, demonstrated significant neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model, ameliorating motor complications in patients with advanced Parkinson's disease.

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.

Bumetanide (PF 1593) is a potent sulfamoylanthranilic acid derivative belonging to the class of loop diuretics. In the brain, bumetanide may prevent seizures in neonates by blocking the bumetanide-sensitive sodium-potassium-chloride cotransporter (NKCC1), thereby inhibiting chloride uptake thus, decreasing the internal chloride concentration in neurons and may block the excitatory effect of GABA in neonates.

Pramipexole (SND 919) is a selective dopamine receptor agonist used in the therapy of Parkinson disease. Pramipexole therapy is associated with a low rate of transient serum enzyme elevations during treatment but has not been implicated in cases of clinically apparent acute liver injury.

Pramipexole dihydrochloride hydrate (Mirapex) is the hydrochloride salt of pramipexole, a benzothiazole derivative. As a nonergot dopamine agonist, pramipexole binds to D2 and D3 dopamine receptors in the striatum and substantia nigra of the brain.

The quinuclidine PHA 568487 free base is an agonist of the alpha 7 nicotinic acetylcholine receptor that was designed to mitigate the bioactivation associated with the core scaffold and subsequently remove associated liabilities with in vivo tolerability.

SMND-309, a metabolite of salvianolic acid B, exhibits neuroprotective effects in cultured neurons and in rats subjected to permanent middle cerebral artery occlusion.

Neuroprotective agent 6 (Compound Y12) functions as an antioxidant and displays prominent neuroprotective effects in both oxygen-glucose deprivation/reperfusion (OGD/R) induced cell models and transient middle cerebral artery occlusion (tMCAO) induced animal models. Additionally, this compound shows significant metal chelating activity towards Cu2+.

TREK inhibitor-3 (Cpd8l) is a selective inhibitor of TREK-1 that can cross the blood-brain barrier, with an IC50 of 0.81 μM. It offers neuroprotective effects by significantly reducing cortical neuron death induced by oxygen-glucose deprivation/reoxygenation (OGD/R) and alleviating brain injury in middle cerebral artery occlusion/reperfusion (MCAO/R) model mice. TREK inhibitor-3 is utilized in ischemic stroke research.

P2Y1 antagonist 3 (compound 36b) is a P2Y1 antagonist capable of penetrating the blood-brain barrier (BBB), with an IC50 value of 0.50 μM. In a rat middle cerebral artery occlusion (MCAO) model, it demonstrates protective properties and exhibits neuroprotective effects against oxidative stress by upregulating Nrf2 protein levels.

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.

Nrf2 activator-21 is a compound that serves as an Nrf2 activator with both antioxidant and neuroprotective properties. It binds to the Keap1Kelch domain, disrupting the Keap1-Nrf2 interaction and activating antioxidant defense mechanisms. Nrf2 activator-21 decreases apoptosis of hippocampal neurons and reduces caspase-3 activity. It targets cerebral ischemia/reperfusion injury (CIRI) by activating the Nrf2 pathway. The compound improves neurological function, alleviates anxiety-like behavior induced by bilateral carotid artery occlusion (2VO) in rats, and enhances memory. Nrf2 activator-21 is applicable in studies of cerebral ischemia/reperfusion injury.

TRPM2-IN-2 is a potent and selective TRPM2 inhibitor (IC50= 0.66 μM) with minimal activity against TRPM8 and TRPV1 (IC50> 10 μM). It demonstrates significant neuroprotective effects in both an in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model and an in vivo transient middle cerebral artery occlusion (tMCAO) mouse model. TRPM2-IN-2 can be used for research related to ischemic stroke.

RIPK1-IN-34 is a selective RIPK1 inhibitor capable of penetrating the blood-brain barrier with an IC50 of 126.70 nM, showing minimal inhibition of RIPK3 (IC50 > 10,000 nM). It exerts significant neuroprotective effects by inhibiting the phosphorylation of RIPK1, RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) in the necroptosis pathway. RIPK1-IN-34 demonstrates neuroprotective effects in rat models of middle cerebral artery occlusion (MCAO) and is a candidate for research in the treatment of acute ischemic stroke (AIS).

RIPK1-IN-39 (compound 2) is a potent and selective inhibitor of RIPK1 with an IC50 of 69.40 nM, exhibiting over 100-fold selectivity for RIPK1 over RIPK3 (IC50= 6946 nM). It protects HT-22 and HT-29 cells from necroptosis by inhibiting the phosphorylation and activation of the RIPK1-RIPK3-MLKL pathway. Additionally, RIPK1-IN-39 shows neuroprotective effects in a rat middle cerebral artery occlusion (MCAO) model. This compound is applicable in acute ischemic stroke (AIS) research.

Idebenone-SS-20 (Idebenone-2S-FrFK-NH2) is a derivative of Idebenone conjugated with the mitochondrial-targeting peptide SS-20. It exhibits neuroprotective and anti-inflammatory properties. This compound maintains mitochondrial membrane potential, enhances ATP production, reduces reactive oxygen species (ROS) accumulation, preserves mitochondrial morphology, and increases the NAD+/NADH ratio. In a transient middle cerebral artery occlusion mouse model, Idebenone-SS-20 demonstrates potent neuroprotective effects and can be utilized in studies related to cerebral ischemia-reperfusion injury.

NFI23 is a GluN2B-NMDAR inhibitor with an IC50 of 1.31 μM and a Ki of 5.98 nM. It can cross the blood-brain barrier and binds to the ifenprodil binding site of GluN2B-NMDAR, reducing NMDA-induced Ca2+ influx and reactive oxygen species (ROS) production. It helps maintain mitochondrial membrane potential, inhibits neuronal apoptosis, and restores p-ERK1/2 expression. NFI23 demonstrates neuroprotective effects against NMDA-induced cytotoxicity and in a rat model of middle cerebral artery occlusion (MCAO), making it useful for ischemic stroke research.

KUS121 is a valosin-containing protein modulator that inhibits VCP ATPase activity with an IC50 of 330 nM, suppresses tunicamycin-induced ATP depletion, cell death, and CHOP upregulation in HeLa cells, protects primary cortical neurons from oxygen-glucose deprivation injury in vitro, reduces infarct volume and improves motor performance in mouse models of focal cerebral ischemia, and preserves retinal structure and visual function in rd10 retinitis pigmentosa models, supporting its investigation in neuroprotection and ischemic disease research.

L-Palmitoylcarnitine chloride (Palmitoyl-L-carnitine chloride) is a fatty acid metabolite with antithrombotic properties that protects mice from ischemic stroke by counteracting intracerebral thrombosis in the tMCAO model.L-Palmitoylcarnitine chloride (Palmitoyl-L-carnitine chloride) is a fatty acid metabolite with antithrombotic properties. Palmitoylcarnitine chloride inhibits the Na/K pump in the heart and inhibits FeCl 3-induced arterial thrombosis Attenuates intracerebral thrombosis and inflammation in a mouse model of transient middle cerebral artery occlusion (tMCAO).

LFHP-1c is a novel PGAM5 inhibitor that shows neuroprotective activity in an ischemic stroke model, preventing BBB destruction after transient middle cerebral artery occlusion (tMCAO) in rats.LFHP-1c can be used to study cerebral ischemic stroke.

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.

Myelin oligodendrocyte glycoprotein (MOG) peptide, a truncated form of MOG located on the extracellular myelin sheath surface, interacts with antigen serotype HLA-DR2 to mitigate effects of ischemic stroke induced by middle cerebral artery occlusion (MCAO) in mice. In female mice, it notably reduces cortical and striatal infarct volumes, lessens sensorimotor deficits as observed in tube- and corner turn tests, enhances engagement with novel odors, and prolongs the duration of cage mate-directed vocalizations, without exhibiting similar outcomes in male mice.