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.

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

PDE2 inhibitor6 (Compound 1) is an orally active phosphodiesterase (PDE) inhibitor, effectively inhibiting PDE2A, PDE3B, and PDE10A2 with IC50 values of 0.95 nM, 6.17 μM (pIC50=5.21), and 87.1 nM (pIC50=7.06), respectively. It modulates AMPA receptor activity, enhances synaptic plasticity, and improves learning and memory in rat models. Furthermore, PDE2 inhibitor6 possesses blood-brain barrier permeability.

Progranulin modulator-2 (compound 18A) is a novel bromodomain and extra-terminal domain (BET) inhibitor. By targeting BET protein family members, Progranulin modulator-2 enhances PGRN expression. It is applicable for studying the role of BET proteins in neurodevelopment, neural plasticity, and neurodegeneration.

PDE1-IN-11 is a potent and selective PDE1 inhibitor. It enhances synaptic plasticity and cerebral blood flow by elevating cAMP/cGMP levels, used for cognitive enhancement research.

(E/Z)-Oleamide (Octadec-9-enamide) is a PPARα ligand found in the hippocampus. It can be isolated from the plant Galium aparineL. (GA). (E/Z)-Oleamide regulates hippocampal plasticity by transcriptional activation of CREB and influences feeding and sexual behavior in rats.

KMCA-0011 is an orally active antagonist of the ɑ2C adrenoceptor (Ki= 56.7 nM). It alleviates depressive behavior by enhancing brain-derived neurotrophic factor (BDNF) and synaptic plasticity. KMCA-0011 demonstrates excellent metabolic stability, maintaining 99.8% plasma stability after 120 minutes. It is a useful compound for researching depression.

NSD2-IN-6 is a selective inhibitor of NSD2, with an IC50 of 3.8 nM for NSD2 and 274 nM for NSD1. It reduces H3K36me2 levels and reverses cellular plasticity by restoring androgen receptor (AR) signaling pathways. In organoid models, NSD2-IN-6 prompts a transition of cell states from cluster 2 and cluster 3 to cluster 1. In vivo, it exhibits antitumor activity by reversing tumor cell plasticity, inhibiting growth, and promoting apoptosis. NSD2-IN-6 is useful for research in prostate cancer.

ACDPP is a specific antagonist of metabotropic glutamate receptor 5 (mGluR5) that partially blocks the DHPG-induced increase of fragile X mental retardation protein (FMRP), ACDPP is used as a pharmacological tool in neuroscience research to study group I mGluR signaling, synaptic plasticity, and molecular mechanisms underlying fragile X syndrome.

GNE-140 is a novel and potent lactate dehydrogenase A (LDHA) inhibitor that disrupts glycolytic metabolism in MIA PaCa-2 human pancreatic cancer cells, inducing rapid metabolic reprogramming prior to delayed cell death, with intrinsic resistance observed in OXPHOS-dependent pancreatic cell lines that can be reversed by phenformin, while acquired resistance is driven by AMPK-mTOR-S6K pathway activation, highlighting its value for studying metabolic plasticity and therapeutic resistance.

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.

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

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].

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].