neuron-2

Branaplam (LMI 070) is a highly potent, selective and orally active small molecule SMN2 splicing modulator.

1-Aminocyclopropane-1-carboxylic acid (ACC) is an intermediate in the synthesis of ethylene, the plant hormone responsible for biological processes ranging from seed germination to organ senescence. It is a small molecule agonist at the glycine modulatory site of the NMDA receptor (EC50 = 0.7-0.9 μM) in the presence of low levels (1 μM) of glutamate and as a competitive antagonist at the glutamate-binding site on NMDA receptors (EC50 = 81.6 nM) with high levels (10 μM) of glutamate.2 This compound has been reported to protect against neuron cell death in vivo models of ischemia by enabling moderate levels of NMDA receptor activation and attenuating any excess NMDA receptor signaling that may lead to neurotoxicity.

Olodanrigan (EMA401), a highly selective AT2R antagonist, inhibition of augmented AngII AT2R induced p38 and p42 p44 MAPK activation, and hence inhibition of DRG neuron hyperexcitability and sprouting of DRG neurons. EMA401 blocks p38, p42 p44 mitogen-activated protein kinase (MAPK) activation, neurite outgrowth in adult rat DRG neurons, and sensitization of adult rat and human DRG neurons induced by AngII. It inhibits capsaicin responses in cultured hDRG neurons.

Palmitic acid-13C is intended for use as an internal standard for the quantification of palmitic acid by GC- or LC-MS. Palmitic acid is a 16-carbon saturated fatty acid. It comprises approximately 25% of human total plasma lipids.1 It increases protein levels of COX-2 in RAW 264.7 cells when used at a concentration of 75 μM.2 Palmitic acid is involved in the acylation of proteins to anchor membrane-bound proteins to the lipid bilayer.2,3,4,5,6 |1. Santos, M.J., López-Jurado, M., Llopis, J., et al. Influence of dietary supplementation with fish oil on plasma fatty acid composition in coronary heart disease patients. Ann. Nutr. Metab. 39(1), 52-62 (1995).|2. Lee, J.Y., Sohn, K.H., Rhee, S.H., et al. Saturated fatty acids, but not unsaturated fatty acids, induced the expression of cyclooxygenase-2 mediated through toll-like receptor 4. J. Biol. Chem. 276(20), 16683-16689 (2001).|3. Dietzen, D.J., Hastings, W.R., and Lublin, D.M. Caveolin is palmitoylated on multiple cysteine residues. Palmitoylation is not necessary for localization of caveolin to caveolae. J. Biol. Chem. 270(12), 6838-6842 (1995).|4. Robinson, L.J., and Michel, T. Mutagenesis of palmitoylation sites in endothelial nitric oxide synthase identifies a novel motif for dual acylation and subcellular targeting. Proc. Nat. Acad. Sci. USA 92(25), 11776-11780 (1995).|5. Topinka, J.R., and Bredt, D.S. N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+ channel Kv1.4. Neuron 20(1), 125-134 (1998).|6. Miggin, S.M., Lawler, O.A., and Kinsella, B.T. Palmitoylation of the human prostacyclin receptor. Functional implications of palmitoylation and isoprenylation. J. Biol. Chem. 278(9), 6947-6958 (2003).

1. Acetylcorynoline (O-Acetylcorynoline) has antifungal,anti-inflammatory activity. 2. Acetylcorynoline may be one of the potent immunosuppressive agents through the blockage of dendritic cells maturation and function. 3. Acetylcorynoline is potential as a possible antiparkinsonian drug. (1) Significantly decreases dopaminergic neuron degeneration induced by 6-hydroxydopamine in BZ555 strain; (2) Prevents α-synuclein aggregation; (3) Restores food-sensing behavior, and dopamine levels; (4) Prolongs life-span in 6-hydroxydopamine-treated N2 strain. 4. Acetylcorynoline may exert its effects by decreasing egl-1 expression to suppress apoptosis pathways and by increasing rpn5 expression to enhance the activity of proteasomes.

PA22-2 (free acid) (Cys-Laminin A chain 2091-2108), a peptide, promotes neurite outgrowth and facilitates the formation of neuron-like processes. It is used in the culturing of human adenoid cystic carcinoma cells and the development of peptide-functionalized supported phospholipid bilayers [1] [2] [3].

Palmitic acid-13C is intended for use as an internal standard for the quantification of palmitic acid by GC- or LC-MS. Palmitic acid-13C contains 13C at the C2 position and has been used in the study of free fatty acid incorporation into phospholipid fatty acids in soil microbes.1 Palmitic acid is a 16-carbon saturated fatty acid. It comprises approximately 25% of human total plasma lipids.2 It increases protein levels of COX-2 in RAW 264.7 cells when used at a concentration of 75 μM.3 Palmitic acid is involved in the acylation of proteins to anchor membrane-bound proteins to the lipid bilayer.3,4,5,6,7 |1. Dippold, M.A., and Kuzyakov, Y. Direct incorporation of fatty acids into microbial phospholipids in soils: Position-specific labeling tells the story. Geochim. Cosmochim. Acta 174(1), 211-221 (2016).|2. Santos, M.J., López-Jurado, M., Llopis, J., et al. Influence of dietary supplementation with fish oil on plasma fatty acid composition in coronary heart disease patients. Ann. Nutr. Metab. 39(1), 52-62 (1995).|3. Lee, J.Y., Sohn, K.H., Rhee, S.H., et al. Saturated fatty acids, but not unsaturated fatty acids, induced the expression of cyclooxygenase-2 mediated through toll-like receptor 4. J. Biol. Chem. 276(20), 16683-16689 (2001).|4. Dietzen, D.J., Hastings, W.R., and Lublin, D.M. Caveolin is palmitoylated on multiple cysteine residues. Palmitoylation is not necessary for localization of caveolin to caveolae. J. Biol. Chem. 270(12), 6838-6842 (1995).|5. Robinson, L.J., and Michel, T. Mutagenesis of palmitoylation sites in endothelial nitric oxide synthase identifies a novel motif for dual acylation and subcellular targeting. Proc. Nat. Acad. Sci. USA 92(25), 11776-11780 (1995).|6. Topinka, J.R., and Bredt, D.S. N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+ channel Kv1.4. Neuron 20(1), 125-134 (1998).|7. Miggin, S.M., Lawler, O.A., and Kinsella, B.T. Palmitoylation of the human prostacyclin receptor. Functional implications of palmitoylation and isoprenylation. J. Biol. Chem. 278(9), 6947-6958 (2003).

SMN2-Stablizer-27 is a stablizer of survival of motor neuron 2 (SMN2), and a post-translationally stablizing SMN protein for the treatment of spinal muscular atrophy (SMA).

16F16 is a protein disulfide isomerase (PDI) inhibitor.1It inhibits PDI reductase activity in an enzyme assay when used at concentrations ranging from 1 to 100 μg/ml.116F16 reduces PC12 cell apoptosis induced by the misfolded huntingtin protein HTTQ103. It suppresses PDI-dependent mitochondrial outer membrane permeabilization (MOMP) in isolated PC12 cell mitochondria. 16F16 (2, 3, 4, and 10 μM) reduces HTTN90Q73mutant huntingtin-induced medium spinal neuron death and MOMP in rat corticostriatal slices. It also reduces pyramidal neuron death induced by amyloid-β precursor protein (APP) in rat corticostriatal slices. 1.Hoffstrom, B.G., Kaplan, A., Letso, R., et al.Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteinsNat. Chem. Biol.6(12)900-906(2010)

KPZ560, a potent HDAC 1 and HDAC 2 inhibitor, exhibits IC50 values of 12 nM and 68 nM, respectively. This compound enhances spine density in mouse granule neuron dendrites and inhibits growth in the MCF-7 breast cancer cell line [1].

3'-Methoxypuerarin shows neuron protection activity, it can protect hippocampal neurons against ischemia reperfusion injury by inhibiting apoptosis. 3'-Methoxypuerarin(3'- Methoxy Puerarin) has antioxidant activities, it shows ONOO(-) scavenging activity and weak NO· and O(2)(-) scavenging activities.

Photoswitchable Kv channel blocker (IC50 values are 2 and 64 μM at 500 nm and 380 nm respectively). Switches conformation from cis to trans at 500 nm and trans to cis at 380 nm. Exhibits minimal activity at Nav1.2 and L-type Ca2+ channels. Stimulates action potential firing of hippocampal neurons in vitro at 500 nm and restores visual responsiveness in blind mice at 380 nm. Fortin et al (2008) Photochemical control of endogenous ion channels and cellular excitability. Nat.Methods 5 331 PMID:18311146 |Polosukhina et al (2012) Photochemical restoration of visual responses in blind mice. Neuron 75 271 PMID:22841312 |Banghart et al (2009) Photochromic blockers of voltage-gated potassium channels. Angew.Chem.Int.Ed. 48 9097 PMID:19882609

Rasagiline-13C3is intended for use as an internal standard for the quantification of rasagiline by GC- or LC-MS. Rasagiline is an inhibitor of monoamine oxidase B (MAO-B; IC50= 4.43 nM for the rat brain enzyme).1It is selective for MAO-B over MAO-A (IC50= 412 nM for the rat brain enzyme). It inhibits serum and NGF withdrawal-induced apoptosis of PC12 cells when used at concentrations ranging from 0.01 to 100 μM.2Rasagiline inhibits rat brain MAO-Bin vivo(ED50= 0.1 mg/kg).1It reduces cerebral edema in a mouse model of traumatic brain injury.2Rasagiline (0.1 mg/kg) reduces cortical and hippocampal levels of full-length and soluble amyloid precursor protein (APP) in rats and mice. It also reduces α-synuclein-induced substantia nigral neuron loss and improves motor dysfunction in a mouse model of Parkinson's disease.3Formulations containing rasagiline have been used in the treatment of Parkinson's disease. 1.Youdim, M.B.H., Gross, A., and Finberg, J.P.Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase BBrit. J. Pharmacol.132(2)500-506(2001) 2.Youdim, M.B.H., and Weinstock, M.Molecular basis of neuroprotective activities of rasagiline and the anti-Alzheimer drug TV3326 [(N-propargyl-(3R) aminoindan-5-YL)-ethyl methyl carbamate]Cell. Mol. Neurobiol.21(6)555-573(2001) 3.Kang, S.S., Ahn, E.H., Zhang, Z., et al.α-Synuclein stimulation of monoamine oxidase-B and legumain protease mediates the pathology of Parkinson's diseaseEMBO J.37(12)e98878(2018)

TREK1 and TREK2 channel activator (EC50 = 0.76 μM in Rb efflux assay in TREK1-expressing CHO cells). Exhibits selectivity for TREK1/2 over TRAAK, TASK3 and a range of other potassium channels. Hyperpolarizes membrane potential of dorsal root ganglion neurons and depresses neuronal activity in vitro. Loucif et al (2018) GI-530159, a novel, selective, mechanosensitive two-pore-domain potassium (K2P) channel opener, reduces rat dorsal root ganglion neuron excitability. Br.J.Pharmacol. 175 2272 PMID:29150838