occlusion

TGX-115 is a cell-permeable and potent inhibitor of the PI 3-K isoform p110β p110δ (IC50 values of 0.13 μM for p110β and 0.63 μM for p110δ), an enzyme that regulates platelet adhesion and inhibits phosphoinositide (PI) 3-kinase, and can be used to treat coronary artery occlusion, stroke, acute coronary artery It can be used to treat cardiovascular diseases such as coronary occlusion, stroke, acute coronary syndrome, acute myocardial infarction, restenosis, atherosclerosis and unstable angina.

Lifarizine (RS-87476), a calcium-sodium channel antagonist, shows neuroprotective activity in a simplified rat survival model of double vessel occlusion.

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.

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.

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.

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.

MTP 131 is a mitochondria-targeted peptide antioxidant.1,2It localizes to the mitochondria and reducestert-butyl hydroperoxide-induced lipid peroxidation and apoptosis in SH-SY5Y cells when used at concentrations ranging from 0.001 to 1 nM.1MTP 131 (2 mg kg) reduces infarct volume, hemispheric swelling, and glutathione (GSH) depletion in a mouse model of acute cerebral ischemia induced by middle cerebral artery occlusion (MCAO).2It increases survival, improves motor function, and decreases degeneration of the lumbar spinal cord in a superoxide dismutase 1 mutant (SOD1G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS) when administered at a dose of 5 mg kg. MTP 131 reduces albuminuria, urinary hydrogen peroxide levels, and mesangial matrix accumulation, as well as preserves superoxide production, in adb dbmouse model of diabetic nephropathy.3 1.Zhao, K., Luo, G., Giannelli, S., et al.Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell linesBiochem. Pharmacol.70(12)1796-1806(2005) 2.Szeto, H.H.Mitochondria-targeted peptide antioxidants: Novel neuroprotective agentsAAPS J.8(3)E521-E531(2006) 3.Miyamoto, S., Zhang, G., Hall, D., et al.Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protects db db mice against progression of diabetic kidney diseaseJ. Biol. Chem.295(21)7249-7260(2020)

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

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.

Coumetarol (Dicumoxane) is a vitamin K antagonist and an oral anticoagulant that can be used to study arterial thrombotic occlusion.

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+.

ASP8731 is a selective inhibitor of BACH1 that prevents inflammation and vascular occlusion, and induces fetal hemoglobin in sickle cell disease.

Fostedil is a calcium channel antagonist. KB-944 increased regional segment function in normal and ischemic regions and maintained distal coronary artery perfusion pressure, coronary flow and transmural regional myocardial blood flow during partial corona

LY 215490 is a selective, competitive and systemically active antagonist of AMPA receptor. LY 215490 has neuroprotective effect against focal ischaemia in a model of permanent MCA occlusion in the rat.

TCV-309 is an inhibitor of platelet activating factor (PAF). TCV-309 reduces graft PMN infiltration and enhances early function of 24-hour-preserved rat kidneys with long warm ischemia. TCV-309 attenuates the priming effects of bronchoalveolar macrophages

Porfimer sodium is t he sodium salt of a mixture of oligomers formed by ether and ester linkages of up to eight porphyrin units with photodynamic activity. Absorbed selectively by tumor cells, porfimer produces oxygen radicals after activation by 630 nm w

(±)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).

Thrombin receptor peptide ligand is antagonist of the thrombin receptor (EC50s = 16-33 μM to inhibit platelet aggregation in vitro). It inhibits α-thrombin and platelet aggregation induced by thrombin receptor activating peptide in vitro when used at a concentration of 32 μM but does not affect platelet aggregation induced by ADP or collagen. It also inhibits thrombin- and TRAP-induced proliferation of vascular smooth muscle cells (VSMCs). Thrombin receptor peptide ligand (100 μmol/kg bolus, i.v., plus 900 μmol/kg infusion) inhibits arterial thrombosis in a rabbit model of partial carotid artery occlusion without increasing bleeding time.

KUS121 is a valosin-containing protein (VCP) modulator that inhibits VCP ATPase activity (IC50= 330 nM).1It inhibits cell death, ATP depletion, and upregulation of C/EBP-homologous protein (CHOP) induced by tunicamycin, an inducer of ER stress, in HeLa cells when used at concentrations of 20, 50, and 50 μM, respectively. KUS121 (100 μM) inhibits ATP depletion and cell death induced by oxygen-glucose deprivation (OGD) in rat primary cortical neurons in anin vitromodel of cerebral ischemia.2It reduces infarction volume and increases the latency to fall in an accelerating rotarod test in a mouse model of focal cerebral ischemia induced by transient distal middle cerebral artery occlusion (MCAO) when administered at a dose of 100 mg/kg immediately following occlusion and again at 50 mg/kg following reperfusion. KUS121 (50 mg/kg) inhibits thinning of the retinal outer nuclear layer and preserves visual function in an rd10 mouse model of retinitis pigmentosa.1 1.Ikeda, H.O., Sasaoka, N., Koike, M., et al.Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosaSci. Rep.45970(2014) 2.Kinoshita, H., Maki, T., Yasuda, K., et al.KUS121, a valosin-containing protein modulator, attenuates ischemic stroke via preventing ATP depletionSci. Rep.9(1)11519(2019)

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)

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).