plasticity

ZD7288 (ICI D7288), a selective hyperpolarization-activated cyclic nucleotide-gated channel blocker, inhibits hippocampal synaptic plasticity.

Rhosin hydrochloride is a specific inhibitor of the RhoA subfamily Rho GTPases and inhibits the RhoA-GEF interaction. Rhosin hydrochloride can significantly induce cell apoptosis without affecting cell cycle progression. [1]

Cardiogenol C is a cardiomyogenesis inducer in embryonic stem cells.

Cutamesine dihydrochloride (SA4503 dihydrochloride) is a selective σ1 receptor agonist (IC50: 17.4 nM). It shows selectivity for σ1 over σ2 receptors, and inhibits angiotensin II-induced cardiomyocyte hypertrophy in vitro and attenuates myocardial hypertrophy in vivo. In a rat model of experimental stroke, it enhances brain plasticity and sensorimotor function.

Afizagabar (S44819) is a first-in-class, competitive, and selective antagonist at the GABA-binding site of the α5-GABAAR, with an IC50 of 585 nM for α5β2γ2 and a Ki of 66 nM for α5β3γ2. It enhances hippocampal synaptic plasticity and exhibits pro-cognitive efficacy [1].

Ganglioside GM1is a monosialylated ganglioside and the prototypic ganglioside for those containing one sialic acid residue.1,2It is found in a large variety of cells, including immune cells and neurons, and is enriched in lipid rafts in the cell membrane.3It associates with growth factor receptors, including TrkA, TrkB, and the GDNF receptor complex containing Ret and GFRα, and is required for TrkA expression on the cell surface. Ganglioside GM1interacts with other proteins to increase calcium influx, affecting various calcium-dependent processes, including inducing neuronal outgrowth during differentiation. Ganglioside GM1acts as a receptor for cholera toxin, which binds to its oligosaccharide group, facilitating toxin cell entry into epithelial cells of the jejunum.4,5Similarly, it is bound by the heat-labile enterotoxin fromE. coliin the pathogenesis of traveler's diarrhea.6Ganglioside GM1gangliosidosis, characterized by a deficiency in GM1-β-galactosidase, the enzyme that degrades ganglioside GM1, leads to accumulation of the gangliosides GM1and GA1in neurons and can be fatal in infants.1Levels of ganglioside GM1are decreased in the substantia nigra pars compacta in postmortem brain from patients with Parkinson's disease.3Ganglioside GM1mixture contains a mixture of ovine ganglioside GM1molecular species with primarily C18:0 fatty acyl chain lengths, among various others. [Matreya, LLC. Catalog No. 1544] 1.Kolter, T.Ganglioside biochemistryISRN Biochem.506160(2012) 2.Mocchetti, I.Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophinsCell Mol. Life Sci.62(19-20)2283-2294(2005) 3.Ledeen, R.W., and Wu, G.The multi-tasked life of GM1 ganglioside, a true factotum of natureTrends Biochem. Sci.40(7)407-418(2015) 4.Turnbull, W.B., Precious, B.L., and Homans, S.W.Dissecting the cholera toxin-ganglioside GM1 interaction by isothermal titration calorimetryJ. Am. Chem. Soc.126(4)1047-1054(2004) 5.Blank, N., Schiller, M., Krienke, S., et al.Cholera toxin binds to lipid rafts but has a limited specificity for ganglioside GM1Immunol. Cell Biol.85(5)378-382(2007) 6.Minke, W.E., Roach, C., Hol, W.G., et al.Structure-based exploration of the ganglioside GM1 binding sites of Escherichia coli heat-labile enterotoxin and cholera toxin for the discovery of receptor antagonistsBiochemistry38(18)5684-5692(1999)

Highly potent and selective group II metabotropic glutamate receptor antagonist. Disodium salt of LY 341495 Fitzjohn et al (1998) The potent mGlu receptor antagonist LY341495 identifies roles for both cloned and novel mGlu receptors in hippocampal synaptic plasticity. Neuropharmacology 37 1445 PMID:9886667 |Ornstein et al (1998) 2-Substituted (2SR)-2-amino-2-((1SR,2SR)-2-carboxycycloprop-1-yl) glycines as potent and selective antagonists of group II metabotropic glutamate receptors. 2. Effects of aromatic substitution, pharmacological characterization, and bioav J.Med.Chem. 41 358 PMID:9464367 |Johnson et al (1999) [3H]-LY341495 as a novel antagonist radioligand for group II metabotropic glutamate receptors: characterization of binding to membranes of mGlu receptor subtype expressing cells. Neuropharmacology 38 1519 PMID:10530814

NVS-BET-1 is a BET bromodomain inhibitor that can regulate keratinocyte plasticity.

AMPA-IN-1 is a potent inhibitor of AMPA receptors, widely expressed in the brain and central to the regulation of rapid excitatory synaptic transmission and synaptic plasticity. [14]

NCI-006 is a potent new inhibitor of lactate dehydrogenase (LDH) that disrupts tumor growth in mice. LDH inhibition slows tumor growth but rapidly redirects pyruvate to support mitochondrial metabolism. Inhibiting both mitochondrial complex 1 and LDH suppresses metabolic plasticity of glycolytic tumors in vivo, significantly prolonging tumor growth inhibition.

PDE1-IN-1can enhance levels of the second messengers cAMP cGMP leading to the expression of neuronal plasticity-related genes, neurotrophic factors, and neuroprotective molecules. These neuronal plasticity enhancement properties make PDE1 inhibitors good candidates as therapeutic agents in many neurological conditions.

Neurogranin (48-76), mouse, is a peptide comprising residues 48-76 of Neurogranin, a post-synaptically exclusive calmodulin-binding protein that mediates NMDAR-driven synaptic plasticity by regulating the calcium-calmodulin (Ca2+-CaM) pathway [1].

Leptin (116-130), a bioactive fragment of leptin, enhances synaptic plasticity in the hippocampus by promoting AMPA receptor trafficking to synapses. It preserves hippocampal synapse integrity and prevents neuronal cell death in amyloid toxicity models, showing promise for Alzheimer's disease (AD) research [1].

Cardiogenol C hydrochloride (Cardiogenol C) can induces the differentiation of ESCs into cardiomyocytes (EC50= 100 nM).

Gangliotetraose (Gg4), a tetrasccharide, predominantly comprises GM1 and its sialylated derivatives, which play a crucial role in modulating nuclear Ca2+ efflux and maintaining lower nuclear Ca2+ levels in differentiated neurons. Moreover, GM1 influences neuronal plasticity, repair mechanisms, and neurotrophin release in the brain [1] [2].

CPF-7 (Caerulein precursor fragment), an insulinotropic peptide, promotes insulin secretion and drives epithelial-mesenchymal transition via Snai1 upregulation in PANC-1 ductal cells. Moreover, it induces exocrine plasticity through Ngn3 upregulation, with applications in type 2 diabetes research [1] [2].

DU-14, a powerful steroid sulfatase inhibitor, has an IC 50 of 55.8 nM and effectively inhibits MCF-7 cell proliferation with an IC 50 of 38.7 nM. It exhibits neuroprotective properties against neurotoxic Aβ, indicating that by increasing endogenous DHEAS, DU-14 could help alleviate Aβ-induced issues in spatial memory and synaptic plasticity [1] [2] [3].

Sp-8-pCPT-cGMPS is a potent agonist for cyclic guanosine monophosphate-gated (CNG) channels and serves as a lipophilic activator for PKG (types I α, I β, and II) and PKA II. It exhibits excellent cell membrane permeability and stability against phosphodiesterases. This compound is utilized in studying the role of cGMP in synaptic transmission and neural plasticity.

8-pCPT-cGMP-AM (8-(4-Chlorophenylthio)-cGMP-AM) is a highly membrane-permeable prodrug of the PKG agonist 8-pCPT-cGMP, designed to enhance membrane permeability of cGMP. It is converted into its active form within the cell via esterase hydrolysis, thus activating PKG. This compound is utilized to investigate the role of cGMP signaling in neural plasticity and memory formation.

TAT-DEF-Elk-1 TFA is a cell-penetrating peptide Elk-1 inhibitor, mimics and specifically interferes with the DEF domain of Elk-1. TAT-DEF-Elk-1 blocks Elk-1 phosphorylation and prevents Elk-1 nuclear translocation without interfering with ERK nor MSK1 act

CMX-8933 is an 8-peptide fragment of the goldfish brain neurotrophic ependymin protein. This compound enhances the enzymatic activity of c-Jun N-terminal kinase (JNK), promotes the phosphorylation of JNK and c-Jun proteins, and increases the cellular levels of c-Jun and c-Fos mRNA. CMX-8933 is utilized for investigating the role of ependymin proteins in neural plasticity, learning, memory formation, and neural regeneration.

Pep63, a neuroprotective peptide (VFQVRARTVA), enhances synaptic plasticity and memory. It competitively binds with Aβ1-42 oligomers, thereby inhibiting the formation of Aβ fibrils. Pep63 is employed in research focused on Alzheimer's disease (AD).