Home PI3K/Akt/mTOR GSK-3 Inhibiteur TWS119

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TWS119 GSK-3 Inhibiteur

Réf. Catalogue: S1590

Le TWS119 est un inhibiteur de la GSK-3β avec une IC50 de 30 nM dans un essai acellulaire; ce composé est capable d'induire la différenciation neuronale et peut être utile à la biologie des cellules souches. L'inhibition de la GSK-3β par ce produit chimique déclenche l'autophagy.
TWS119 GSK-3 Inhibiteur Chemical Structure

Structure chimique

Poids moléculaire: 318.33

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Contrôle Qualité (Quality Control)

Lot : Pureté : 99.76%
99.76

Culture cellulaire, traitement et concentration de travail
(Cell Culture, Treatment & Working Concentration)

Lignées cellulaires Type d'essai Concentration Temps d'incubation Formulation Description de l'activité PMID
RAW 264.7 Cytotoxicity Assay 0-10000ng/ml 24 h induces cell death in a dose dependent manner 24330853
D3 Function assay Binding affinity to GSK-3 beta in mouse D3 cells, IC50=0.03μM. 16408003
D3 Function assay Inhibition of GSK-3 beta in mouse D3 cells, Kd=0.126μM. 16408003
D3 Function assay Inhibition of GSK-3 beta in mouse D3 cells assessed as induction of neuron specific marker neurofilament-M by immunofluorescence method, EC50=1μM. 16408003
D3 Function assay Inhibition of GSK-3 beta in mouse D3 cells assessed as induction of neuron specific marker microtubule-associated protein 2 by immunofluorescence method, EC50=1μM. 16408003
D3 Function assay Inhibition of GSK-3 beta in mouse D3 cells assessed as induction of neuron specific marker beta3-tubulin by immunofluorescence method, EC50=1μM. 16408003
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
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Informations chimiques, stockage et stabilité (Chemical Information, Storage & Stability)

Poids moléculaire 318.33 Formule

C18H14N4O2

 Stockage (À compter de la date de réception)
N° CAS 601514-19-6 Télécharger le SDF Stockage des solutions mères

Synonymes N/A Smiles C1=CC(=CC(=C1)N)C2=CC3=C(N2)N=CN=C3OC4=CC=CC(=C4)O

Solubilité (Solubility)

In vitro
Lot:

DMSO : 64 mg/mL (201.04 mM)
(Le DMSO contaminé par l'humidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Water : Insoluble

Ethanol : Insoluble

Calculateur de molarité

Masse Concentration Volume Poids moléculaire
Calculateur de dilution Calculateur de poids moléculaire

In vivo
Lot:

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant l'expérience)

mg/kg g μL

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter d'abord s'il n'y a pas de formulation in vivo dans la section Solubilité.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter d'abord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouterμL PEG300, mélanger et clarifier, puis ajouterμL Tween 80, mélanger et clarifier, puis ajouter μL ddH2O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouter μL Huile de maïs, mélanger et clarifier.

Note : 1. Veuillez vous assurer que le liquide est clair avant d'ajouter le solvant suivant.
2. Assurez-vous d'ajouter le(s) solvant(s) dans l'ordre. Vous devez vous assurer que la solution obtenue, lors de l'ajout précédent, est une solution claire avant de procéder à l'ajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.

Mécanisme d'action (Mechanism of Action)

Targets/IC50/Ki
GSK-3β
(Cell-free assay)
30 nM
In vitro
Treatment of a monolayer of P19 cells with 1 μM TWS119 causes 30–40% cells to differentiate specifically into neuronal lineages based on counting of TuJ1 positive cells with correct neuronal morphology (up to 60% neuronal differentiation occurred through the standard EB formation protocol with concomitant treatment with this compound). This compound tightly binds to GSK-3β (K D = 126 nM) which is quantified by surface plasmon resonance (SPR) and further demonstrates an IC50 of 30 nM. It is found to potently induces neuronal differentiation in both mouse embryonal carcinoma and ES cells. Treatment with this chemical towards hepatic stellate cells (HSC) leads to reduced b-catenin phosphorylation, induces nuclear translocation of b-catenin, elevates glutamine synthetase production, impedes synthesis of smooth muscle actin and Wnt5a, but promotes the expression of glial fibrillary acidic protein, Wnt10b, and paired-like homeodomain transcription factor 2c. This agent triggers a rapid accumulation of β-catenin (mean 6.8 -fold increase by densitometry), augments nuclear protein interaction with oligonucleotide containing the DNA sequences to which Tcf and Lef bind and sharply up-regulates the expression of Tcf7, Lef1 and other Wnt target genes including Jun, Ezd7 (encoding Frizzled-7), Nlk (encoding Nemo-like kinase). It induces a dose-dependent decrease in T cell-specific killing and IFN-g release associated with the preservation of the ability to produce IL-2. A recent study indicates Wnt signaling is induced in polyclonally activated human T cells by treatment with this compound. These T cells preserve a native CD45RA(+)CD62L(+) phenotype compared with control-activated T cells that progresses to a CD45RO(+)CD62L(-) effector phenotype and this occurs in a dose-dependent manner of this chemical. Its-induced Wnt signaling reduces T cell expansion as a result of a block in cell division, and impairs acquisition of T cell effector function as measured by degranulation and IFN-γ production in response to T cell activation. The block in T cell division may be attributed to reduced IL-2Rα expression in T cells treated with this agent that lowers their capacity to use autocrine IL-2 for expansion.
In vivo
A cell population that expressed low levels of CD44 and high levels of CD62L on the cell surface when 30 mg/kg of TWS119 is administered.
Références
  • [4] https://pubmed.ncbi.nlm.nih.gov/19525962/
  • [5] https://pubmed.ncbi.nlm.nih.gov/22013128/

Applications (Applications)

Méthodes Biomarqueurs Images PMID
Immunofluorescence β-catenin / COX-2
S1590-IF1
30618773
Growth inhibition assay Cell viability
S1590-viability1
19995556