Home PI3K/Akt/mTOR GSK-3 inhibitor TWS119

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TWS119 GSK-3 inhibitor

Cat. No.: S1590

TWS119 is a GSK-3β inhibitor with IC50 of 30 nM in a cell-free assay; this compound is capable of inducing neuronal differentiation and may be useful to stem cell biology. GSK-3β inhibition by this chemical triggers autophagy.
TWS119 GSK-3 inhibitor Chemical Structure

Estructura química

Peso molecular: 318.33

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Control de calidad (Quality Control)

Lote: Pureza: 99.76%
99.76

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Líneas celulares Tipo de ensayo Concentración Tiempo de incubación Formulación Descripción de la actividad 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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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular 318.33 Fórmula

C18H14N4O2

 Almacenamiento (Desde la fecha de recepción)
Nº CAS 601514-19-6 Descargar SDF Almacenamiento de soluciones madre

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

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 64 mg/mL (201.04 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Water : Insoluble

Ethanol : Insoluble

Calculadora de Molaridad

Masa Concentración Volumen Peso molecular
Calculadora de Dilución Calculadora de Peso Molecular

In vivo
Lote:

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

mg/kg g μL

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH2O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción (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.
Referencias
  • [4] https://pubmed.ncbi.nlm.nih.gov/19525962/
  • [5] https://pubmed.ncbi.nlm.nih.gov/22013128/

Aplicaciones (Applications)

Métodos Biomarcadores Imágenes PMID
Immunofluorescence β-catenin / COX-2
S1590-IF1
30618773
Growth inhibition assay Cell viability
S1590-viability1
19995556