Home Stem Cells & Wnt Wnt/beta-catenin Inhibidor ICG-001

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ICG-001 Inhibidor de Wnt/β-catenina

Cat. No.: S2662

ICG-001 antagoniza la transcripción mediada por Wnt/β-catenina/TCF y se une específicamente a la proteína de unión a CREB (CBP) con un IC50 de 3 μM, pero no es el coactivador transcripcional relacionado p300. ICG-001 induce la apoptosis.
ICG-001 Wnt/beta-catenin Inhibidor Chemical Structure

Estructura química

Peso molecular: 548.63

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Control de calidad (Quality Control)

Lote: Pureza: 99.75%
99.75

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This compound and Wnt-C59 inhibit in vitro growth of human cholangiocarcinoma cells and reduce tumor area and number in xenograft and thioacetamide models.

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
SH-SY5Y Apoptosis Assay 50 μm 24 h DMSO blocks the protective effect of melatonin against PrP (106–126)-induced apoptotic signals 25251028
AsPC-1 Growth Inhibition Assay 1-20 μM 2/4/6 d inhibits the cell growth in a dose-dependent manner 25082960
MiaPaCa-2 Growth Inhibition Assay 1-20 μM 2/4/6 d inhibits the cell growth in a dose-dependent manner 25082960
PANC-1 Growth Inhibition Assay 1-20 μM 2/4/6 d inhibits the cell growth in a dose-dependent manner 25082960
L3.6pl Growth Inhibition Assay 1-20 μM 2/4/6 d inhibits the cell growth in a dose-dependent manner 25082960
SH-SY5Y Apoptosis Assay 10 μM 24 h inhibits the neuroprotective effects of hypoxia against PrP (106-126)-mediated neuronal cell death 23900566
HKC-8  Function Assay 10 µM 24 h abolishes β-catenin–mediated RAS induction 25012166
HK-2  Function Assay 10 µM 3 h reduced the expression of TGF-β1, α-SMA, and CTGF after treatment with HHE 23690997
HepT1 Apoptosis Assay 0-100 μM 24 h IC50=34 μM 23266718
HuH6 Apoptosis Assay 0-100 μM 24 h IC50=39 μM 23266718
MCF7 Function Assay 5 μm  inhibits leptin-mediated increased expression of Snail, Slug, and Zeb2 22270359
RLE-6TN  Function Assay 2.5/5/7.5 μM 48 h inhibits TGF-β1-induced α-SMA induction and EMT 22241478
HKC-8 Function Assay 5/10/20 μM 48 h blocks β-catenin-driven gene expression 21816937
SW480 Growth Inhibition Assay 2-100 μM IC50=5.8±0.68 μM 15782138
SW480 Function assay Inhibition of CBP binding to beta-casein in human SW480 cells by immunoblot analysis, IC50 = 1.3 μM. 23232060
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, GI50 = 6.1 μM. 24950489
HepG2 Antiproliferative assay 72 hrs Antiproliferative activity against human HepG2 cells after 72 hrs by MTT assay, GI50 = 12.7 μM. 24950489
LoVo Antiproliferative assay 72 hrs Antiproliferative activity against human LoVo cells after 72 hrs by MTT assay, GI50 = 15.6 μM. 24950489
HT-29 Antiproliferative assay 72 hrs Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay, GI50 = 17.2 μM. 24950489
HT29 Function assay 24 hrs Inhibition of Wnt signaling in human HT29 cells assessed as inhibition of beta-catenin-mediated Tcf/Lef transcriptional activity after 24 hrs by dual luciferase reporter gene assay relative to control, IC50 = 18.7 μM. 24950489
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 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
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
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
LoVo Cytotoxicity assay 10 uM 72 hrs Cytotoxicity against Wnt/beta-catenin signalling dependent human LoVo cells assessed as cell viability at 10 uM after 72 hrs by ATPlite assay ChEMBL
NCI-H1703 Function assay 10 uM 24 hrs Inhibition of TNIK in human NCI-H1703 cells transfected with lentiviral vector 7TFP assessed as reduction of GSK3 inhibitor X activated TNIK-mediated Wnt/TCF/beta-catenin-dependent transcription at 10 uM after 24 hrs by luciferase reporter assay ChEMBL
HCT116 Cytotoxicity assay 10 uM 72 hrs Cytotoxicity against Wnt/beta-catenin signalling dependent human HCT116 cells assessed as cell viability at 10 uM after 72 hrs by ATPlite assay ChEMBL
Haga clic para ver más datos experimentales de líneas celulares

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular 548.63 Fórmula

C33H32N4O4

 Almacenamiento (Desde la fecha de recepción)
Nº CAS 780757-88-2 (relative stereochemistry); 847591-62-2 (absolute stereochemistry) Descargar SDF Almacenamiento de soluciones madre

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 30 mg/mL (54.68 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
CBP
(Cell-free assay)
3 μM
In vitro

ICG-001 has no effect on the related reporter construct, FOPFLASH, which contains mutated TCF sites. After treatment with 25μM of this compound for 8 hours, SW480 cell reduces the steady-state levels of Survivin and Cyclin D1 RNA and protein, both of which can be up-regulated by β-catenin. This compound selectively induces apoptosis in transformed cells but not in normal colon cells, reduces in vitro growth of colon carcinoma cells. It can phenotypically rescue normal nerve growth factor (NGF) -induced neuronal differentiation and neurite outgrowth in the presenilin-1 mutant cells, emphasizing the importance of the TCF/β-catenin signaling pathway on neurite outgrowth and neuronal differentiation. A recent study demonstrates that 5μM of this chemical inhibits leptin-induced EMT, invasion and tumorsphere formation in MCF7 cells.

Ensayo de quinasa
Ensayo de Luciferasa Dual como Reportero
El sistema de ensayo de reportero de luciferasa dual (DLR) proporciona un medio eficiente para realizar ensayos de doble reportero. En el ensayo DLRTM, las actividades de las luciferasas de luciérnaga (Photinus pyralis) y Renilla (Renilla reniformis, también conocida como pluma de mar) se miden secuencialmente a partir de una única muestra. El reportero de luciferasa de luciérnaga se mide primero añadiendo el reactivo de ensayo de luciferasa II (LAR II) para generar una señal luminiscente de tipo “brillo”. Después de cuantificar la luminiscencia de la luciérnaga, esta reacción se extingue y la reacción de la luciferasa de Renilla se inicia añadiendo simultáneamente el reactivo Stop & Glo® al mismo tubo. El reactivo Stop & Glo® también produce una señal de tipo “brillo” de la luciferasa de Renilla, que disminuye lentamente durante la medición. En el sistema de ensayo DLRTM, ambos reporteros producen ensayos lineales con sensibilidades subattomol (<10-18) y sin actividad endógena de ninguno de los reporteros en las células huésped experimentales. Además, el formato integrado del ensayo DLRTM proporciona una cuantificación rápida de ambos reporteros, ya sea en células transfectadas o en reacciones de transcripción/traducción sin células.
In vivo

Administration of a water-soluble analog of ICG-001 for 9 weeks reduces the formation of colon and small intestinal polyps by 42% as effectively as the nonsteroidal antiinflammatory agent, which has consistently demonstrated efficacy in this model. No overt toxicity is detected throughout the course of treatment. In the SW620 nude mouse xenograft model of tumor regression, 150 mg/kg, i.v. of this compound demonstrates a dramatic reduction in tumor volume over the 19-day course of treatment, with no mortality or weight loss. This chemical (5 mg/kg per day) significantly inhibits beta-catenin signaling and attenuates bleomycin-induced lung fibrosis in mice, while concurrently preserving the epithelium.

Referencias
  • [4] https://pubmed.ncbi.nlm.nih.gov/20660310/
  • [5] https://pubmed.ncbi.nlm.nih.gov/34214613/

Aplicaciones (Applications)

Métodos Biomarcadores Imágenes PMID
Western blot SOX-2 / CD44 / Survivin / EGFR / FOXM1 / EZH2 / Vimentin pβ-catenin beta-catenin / F-actin ABC / Beta-catenin / E-cadherin / N-cadherin / MMP-9 / c-MYC / Actin / Histone H3 CCNB1 / Cyclin D1
S2662-WB4
25897700

Preguntas frecuentes (Frequently Asked Questions)

Pregunta 1:
If the compound is stored in DMSO at -80, how long would it be stable? For cell culture, how long should I change for the fresh medium with it?

Respuesta:
It in DMSO solution can be stored at 4 degree for 1 week and -20 degree for 1 month. The best storage condition is solid powder, even at -80 the solution is not stable enough for long term storage. For cell culture, you need change medium every 48h.