primary neurons

Adhesamine, a dumbbell-shaped molecule, plays a crucial role in activating the MAPK FAK pathway, thus promoting mammalian cell adhesion and growth. Additionally, it accelerates the differentiation and enhances the survival of mice hippocampal neurons in primary culture.

Boscalid is a broad-spectrum carboxamide fungicide that inhibits fungal respiration by binding to the ubiquinone site of mitochondrial complex II succinate dehydrogenase.1It suppresses mycelial growth ofS. minorby 87 to 100% and ofS. sclerotiorumby 77 to 100% when used at a concentration of 1 μg ml.2In field studies, boscalid applied at 5.6 μg cm2provides 55.5 and 30.4% disease control for lettuce drop caused byS. minorandS. sclerotiorum, respectively. It decreases cell viability of mouse primary cortical neurons following long-term exposure but is not cytotoxic (LC50= >100 μM for acute and continuous exposure). Formulations containing boscalid have been used in agriculture to prevent fungal growth on crops. 1.Wang, Y., Duan, Y., Wang, J., et al.A new point mutation in the iron-sulfur subunit of succinate dehydrogenase confers resistance to boscalid in Sclerotinia sclerotiorumMol. Plant Pathol.16(7)653-661(2015) 2.Matheron, M.E., and Porchas, M.Activity of boscalid, fenhexamid, fluazinam, fludioxonil, and vinclozolin on growth of Sclerotinia minor and S. sclerotiorum and development of lettuce dropPlant Dis.88(6)665-668(2004)

Sciadopitysin may prevent the development of diabetic osteopathy, it exerts its therapeutic effects via upregulation of mitochondrial biogenesis.Sciadopitysin shows protective effects on antimycin A-induced toxicity in osteoblastic MC3T3-E1 cells, it may

Ziconotide Acetate (107452-89-1 free base) (Prialt) is an analgesic agent and has been used to treat neuropathic and non-neuropathic pain. Ziconotide Acetate (107452-89-1 free base) acts by binding to N-type calcium channels situated on the terminal part of primary afferent neurons of the nociceptive pathway therefore reducing synaptic transmission with potent antinociceptive effects.

C-DIM12 induced expression of Nurr1-regulated genes. C-DIM12 increased expression of transfected human Nurr1, induced Nurr1 protein expression in primary dopaminergic neurons and enhanced neuronal survival from exposure to 6-OHDA.

MSN-125 effectively inhibits Bax Bak-mediated apoptosis in HCT-116, BMK Cells, and primary cortical neurons protect primary neurons against glutamate excitotoxicity. MSN-125 is an effective Bax and Bak oligomerization inhibitor. MSN-125 prevents mitochond

Adhesamine diTFA, a dumbbell-shaped molecule, activates the MAPK FAK pathway. It promotes adhesion and growth in mammalian cells and accelerates differentiation and enhances the survival rate of primary cultured mouse hippocampal neurons.

HZS60 is a brain-penetrant NMDAR TRPM4 inhibitor that shows promise in ameliorating cerebral ischemia. It provides significant neuroprotection against ischemic injury in primary neurons caused by NMDA and oxygen-glucose deprivation reoxygenation. HZS60 demonstrates favorable pharmacokinetic properties and can inhibit cerebral ischemia-reperfusion injury, positioning it as a potential inhibitor for ischemic stroke.

RC574 is an inhibitor of ferroptosis and a derivative of the antioxidant and hypocholesterolemic agent probucol .1It inhibits glutamate-induced cell death in HT22 cells (IC50= 276.2 nM) and mouse primary cortical neurons when used at a concentration of 3 μM. RC574 (3 μM) increases glutathione peroxidase 1 (GPX1) levels and GPX activity, as well as inhibits glutamate-induced mitochondrial superoxide anion production, in HT22 cells. It completely inhibits ferroptosis induced by the GPX4 inhibitor RSL3 in HT22 cells when used at concentrations ranging from 62.5 to 1,000 nM. 1.Bueno, D.C., Canto, R.F.S., de Souza, V., et al.New probucol analogues inhibit ferroptosis, improve mitochondrial parameters, and induce glutathione peroxidase in HT22 cellsMol. Neurobiol.57(8)3273-3290(2020)

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)

Iclepertin (BI-425809) is an orally active and selective inhibitor of glycine transporter protein 1 (GlyT1).Iclepertin is used for the treatment of central nervous system disorders such as Alzheimer;s disease. Iclepertin is used for central nervous system disorders such as Alzheimer;s disease, schizophrenia and cognitive disorders.

8-hydroxy Efavirenz is a major oxidative metabolite of the non-nucleoside reverse transcriptase inhibitor efavirenz . 8-hydroxy Efavirenz is formed when efavirenz is metabolized by the cytochrome P450 (CYP) isoform CYP2B6. It induces apoptosis in rat primary hippocampal neurons and loss of dendritic spines in rat primary hippocampal neuronal cultures when used at a concentration of 0.01 μM.

Amyloid-β (25-35) (Aβ (25-35)) is an 11-residue fragment of the Aβ protein that retains the physical and biological characteristics of the full length peptide. It forms fibrils that react to thioflavin T and Congo red and are organized in a cross-β arrangement of β-strands similar to Aβ (1-40) and Aβ (1-42) fibrils. Aggregated Aβ (25-35) decreases the viability of rat adrenal PC12 cells. It also decreases the viability of primary rat cortical neurons at concentrations ranging from 1 nM to 30 μM. In vivo, intracerebral injection of Aβ (25-35) (20 nmol) in rats induces lesions of neuronal and tissue loss. Aggregated Aβ (25-35) administered intracerebroventricularly to rats induces learning and memory impairments in the Y-maze, novel object recognition, and contextual fear conditioning tests.

Cyclo(L-Phe-L-Val) is a metabolite of the sponge bacterium Pseudoalteromonas sp. NJ6-3-1, capable of autoinducing the production of antibacterial substances active against S. aureus at low cell density. It induces neurite outgrowth and branching of chick cortical neurons in vitro at concentrations of 16 and 32 μM, increases phosphorylation of the PI3K substrate Akt, and this induction can be blocked by the PI3K inhibitor LY294002. Additionally, it enhances axon sprouting of calcitonin gene-related protein positive (CGRP+) primary afferents in the spinal cord post-crush injury and of serotonin neurons in the uninjured spinal cord. Cyclo(L-Phe-L-Val) is also a bitter taste component of cocoa and roasted coffee.

D-DOPA is an enantiomer of the dopamine precursor L-DOPA . It can be converted to L-DOPAviasequential oxidation and transamination, which are mediated by D-amino acid oxidase (DAAO) and DOPA transaminase, respectively, in rat kidney homogenates.1It reduces the number of dopaminergic neurons in primary rat embryonic mesencephalic cultures in a concentration-dependent manner.2Intraventricular administration of D-DOPA (200 μg/animal) increases striatal dopamine levels in rats.3D-DOPA (20 mg/kg, i.p.) induces contralateral turns in a rat model of Parkinson's disease induced by 6-OHDA .4 1.Wu, M., Zhou, X.-J., Konno, R., et al.D-dopa is unidirectionally converted to L-dopa by D-amino acid oxidase, followed by dopa transaminaseClin. Exp. Pharmacol. Physiol.33(11)1042-1046(2006) 2.Ling, Z.-D., Pieri, S.C., and Carvey, P.M.Comparison of the neurotoxicity of dihydroxyphenylalanine stereoisomers in cultured dopamine neuronsClin. Neuropharmacol.19(4)360-365(1996) 3.Karoum, F., Freed, W.J., Chuang, L.-W., et al.D-dopa and L-dopa similarly elevate brain dopamine and produce turning behavior in ratsBrain Res.440(1)190-194(1988) 4.Moses, J., Siddiqui, A., and Silverman, P.B.Sodium benzoate differentially blocks circling induced by D-and L-dopa in the hemi-parkinsonian ratNeurosci. Lett.218(3)145-148(1996)

Prostaglandin D2 ethanolamide (PGD2-EA) is a bioactive lipid produced by the sequential metabolism of anandamide (arachidonoyl ethanolamide) by cyclooxygenase (COX) enzymes, in particular by COX-2, and PGD synthase. The biosynthesis of PGD2-EA from anandamide can also be increased when anandamide metabolism is diminished by deletion of fatty acid amide hydrolase. PGD2-EA is inactive against recombinant prostanoid receptors, including the D prostanoid receptor. It increases the frequency of miniature inhibitory postsynaptic currents in primary cultured hippocampal neurons, an effect which is the opposite of that induced by anandamide.. PGD2-EA also induces apoptosis in colorectal carcinoma cell lines.

EGIS-8332 is a potent and selective non-competitive AMPA receptor antagonist. EGIS-8332 inhibits AMPA kainate ion channels and cell death. EGIS-8332 inhibited AMPA currents in rat cerebellar Purkinje cells and inhibited the AMPA- and quisqualate-induced excitotoxicity in primary cultures of telencephalon neurons (IC(50)=5.1-9.0 microM), in vitro. EGIS-8332 seems suitable for further development for the treatment of epilepsy, ischaemia and stroke based on its efficacy in a variety of experimental disease models, and on its low side effect potential.

GYKI 52466 is an allosteric AMPA receptor antagonist. It selectively inhibits AMPA-induced inward currents (IC50 = 7.5 µM) over NMDA- or GABA-induced inward currents in primary rat hippocampal neurons at 50 µM but also inhibits kainate-induced inward currents in the same cells (IC50 = 11 µM).2 GYKI 52466 (10 µM) reduces the amplitude of spontaneous excitatory postsynaptic currents (EPSCs) in the same cells. It increases the latency to seizure onset and reduces mortality in a rat model of generalized tonic-clonic seizures induced by 4-aminopyridine (4-AP) when administered at doses of 25 and 50 mg kg. GYKI 52466 (30 mg kg) prevents neuronal damage in the CA1 region of the hippocampus in a rat model of global ischemia-reperfusion injury induced by four-vessel occlusion.

PD-85639 is a voltage-gated sodium (Na+) channel blocker (75% in 10 min & >95% in 25 min blockage of Na+ current by 25 μM PD85,639; whole-cell patch clamp using primary rat brain neurons) that is shown to target rat brain Nav1.2 with simultaneous high- and low-affinity modes of binding (EC50 = 56 nM 40% & 20 μM 60% at pH 9.0, 5 nM 28% & 3 μM 72% at pH 7.4, against 2 nM [3H]-PD85,639 for binding rat brain synaptosomes; EC50 = 17 nM 39% & 10 μM 61% using at pH 9.0 using rat brain synaptosome membranes) and a fast kinetic (t1 2 = 1.2 at 4°C, <0.5 min at 25°C), competitive against the local anesthetic Na+ channel blockers tetracaine, bupivacaine, and mepivacaine, as well as Na+ channel activators veratridine and batrachotoxin (K1 = 0.26 μM against 5 nM [3H]-BTX for binding rat neocrotical membranes).

DD04107 is a novel inhibitor of α-calcitonin gene-related peptide (α-CGRP) exocytotic release from primary sensory neurons, selectively interacting with Synaptotagmin 1.

ARN 14494 is a potent serine palmitoyltransferase inhibitor (SPT; IC50 = 27.3 nM). ARN 14494 inhibits synthesis of long chain ceramides and dihydroceramides in an in vitro model of Alzheimer's diease. The compound prevents the synthesis of proinflammatory cytokines and the oxidative stress-related enzymes iNOS and COX-2 in mouse primary cortical astrocytes. ARN 14494 is neuroprotective against β-amyloid 1-42 induced neurotoxicity in primary cortical neurons co-cultured with astrocytes.

Insulin-like Growth Factor II (IGF-2), the primary somatomedin in human serum, exerts both permissive and direct influences on neurite outgrowth and significantly improves the survival of sympathetic and sensory neurons [1] [2].

Tat-NTS peptide, a cell-penetrating compound, comprises the HIV-1 Tat protein transduction domain fused with a 10-amino acid sequence (residues 228-237) from the repeat III domain of annexin A1, serving as a nuclear translocation signal (NTS). This peptide hinders the interaction between annexin A1 and importin β, obstructing annexin A1's nuclear entry in primary mouse hippocampal neurons. Tat-NTS effectively prevents apoptosis triggered by glucose-oxygen deprivation and reperfusion in these neurons. When administered in vivo at a dosage of 10 mg/kg, it significantly reduces infarct size, minimizes neuronal apoptosis, and improves navigation performance in the Morris water maze test for mice subjected to ischemia-reperfusion injury via middle cerebral artery occlusion (MCAO).

Tat-CBD3 is a chemical compound inhibiting the interaction between the N-type voltage-gated calcium channel Cav2.2 and collapsin response mediator protein 2 (CRMP2), as well as the interaction between CRMP2 and the NMDA receptor NR2B subunit. At a concentration of 10 µM, Tat-CBD3 reduces the Cav2.2-CRMP2 interaction by 43% in cell-free assays and impedes the NMDA receptor NR2B subunit-CRMP2 interaction in immunoprecipitation assays. It lowers voltage-induced calcium currents by about 60% in primary rat dorsal root ganglion (DRG) neurons and decreases glutamate-induced cytosolic calcium level rises in primary rat hippocampal neurons. When administered at 20 mg/kg, Tat-CBD3 lessens infarct volume in a rat model of cerebral ischemia following middle cerebral artery occlusion (MCAO). Additionally, intrathecal delivery of Tat-CBD3 at a dose of 20 µg/5 µl mitigates carrageenan-induced thermal hypersensitivity in rats.