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GMX1778 NAMPT inhibidor

Name: GMX1778
Brand: Selleck Chemicals
SKU: S8117
Rating: 5 (8 reviews)

Cat. No.S8117

GMX1778 es un inhibidor potente y específico de la nicotinamida fosforribosiltransferasa (NAMPT) con una IC50 y K_d de < 25 nM y 120 nM, respectivamente. Este compuesto induce la muerte celular programada con características apoptóticas. Fase 1.

GMX1778 NAMPT inhibidor Chemical Structure

Estructura química

Peso molecular: 371.86

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Control de calidad

Lote: S811701 DMSO]74 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Pureza: 99.82%

Citado en Nature Medicine por su máxima calidad
COA
NMR
HPLC
SDS
Hoja de datos

99.82

Dianas relacionadas	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism
Otros NAMPT Inhibidores	OT-82 Padnarsertib (KPT-9274, ATG-019) STF-118804 P7C3 GNE-617 SBI-797812

Cultivo celular, tratamiento y concentración de trabajo

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Descripción de la actividad	PMID
A2780	Cytotoxicity assay		72 hrs	Cytotoxicity against human A2780 cells after 72 hrs by SRB assay, IC50=0.005μM	23617784
NYH	Cytotoxicity assay		3 weeks	Cytotoxicity against human NYH cells after 3 weeks by clonogenic survival assay, LD50=0.0017μM	23679915
A2780	Antiproliferative assay		72 hrs	Antiproliferative activity against human A2780 cells assessed as growth inhibition after 72 hrs by SRB-based microplate reader analysis, IC50=0.005μM	23859118
A2780	Cytotoxicity assay		72 hrs	Cytotoxicity against human A2780 cells assessed as growth inhibition after 72 hrs by WST-1 assay, IC50=0.00056μM	24164086
MCF-7	Cytotoxicity assay		72 hrs	Cytotoxicity against human MCF-7 cells assessed as growth inhibition after 72 hrs by WST-1 assay, IC50=0.0016μM	24164086
HepG2	Function assay		1 hr	Inhibition of NAMPT in human HepG2 cells using [14C]-nicotinamide/PRPP as substrate assessed as formation of [14C]-nicotinamide mononucleotide after 1 hr by liquid scintillation counting analysis, IC50=0.0183μM	24164086
A2780	Antiproliferative assay		72 hrs	Antiproliferative activity against human A2780 cells after 72 hrs by sulforhodamine B assay, IC50=0.005μM	24405419
HONE1	Cytotoxicity assay		24 hrs	Cytotoxicity against human HONE1 cells after 24 hrs by SRB assay, IC50=0.015μM	25147148
MCF	Cytotoxicity assay		24 hrs	Cytotoxicity against human MCF cells after 24 hrs by SRB assay, IC50=0.018μM	25147148
NUGC	Cytotoxicity assay		24 hrs	Cytotoxicity against human NUGC cells after 24 hrs by SRB assay, IC50=0.025μM	25147148
HepG2	Cytotoxicity assay		24 hrs	Cytotoxicity against human HepG2 cells after 24 hrs by SRB assay, IC50=1.245μM	25147148
HA22T	Cytotoxicity assay		24 hrs	Cytotoxicity against human HA22T cells after 24 hrs by SRB assay, IC50=2.067μM	25147148
DLD1	Cytotoxicity assay		24 hrs	Cytotoxicity against human DLD1 cells after 24 hrs by SRB assay, IC50=2.315μM	25147148
A2780	Function assay		72 hrs	Inhibition of NAMPT in human A2780 cells assessed as decrease in cell viability after 72 hrs by SRB assay, IC50=0.001μM	27541271
Rosetta (DE3)	Function assay		15 mins	Inhibition of human full length C-terminal His6-tagged NAMPT expressed in Escherichia coli Rosetta (DE3) cells using nicotinamide as substrate incubated for 15 mins prior to substrate addition measured after 30 mins in presence of PRPP, IC50=0.002μM	27541271
PC3	Antiproliferative assay		5 days	Antiproliferative activity against human PC3 cells assessed as reduction in cell viability incubated for 5 days by Cell-titer Glo reagent based assay, IC50=0.0044μM	28610984
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
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
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 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
U-2 OS	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS 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
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 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
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
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
U-2 OS	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells	29435139
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
4T1	Antitumor assay	10 mg/kg	12 days	Antitumor activity against mouse 4T1 cells implanted in BALB/c mouse assessed as reduction in tumour volume at 10 mg/kg, ip bid for 12 days by vernier caliper method	31400709
4T1	Antitumor assay	10 mg/kg	12 days	Antitumor activity against mouse 4T1 cells implanted in BALB/c mouse assessed as reduction in tumor weight at 10 mg/kg, ip bid for 12 days	31400709
4T1	Antitumor assay	10 mg/kg	12 days	Antitumor activity against mouse 4T1 cells implanted in Balb/c mouse mouse assessed as inhibition of tumor metastasis at 10 mg/kg, ip bid for 12 days measured post last dose by crystal violet staining based thioguanine clonogenic assay	31400709
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Información química, almacenamiento y estabilidad

Peso molecular	371.86	Fórmula	C₁₉H₂₂ClN₅O	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	200484-11-3	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	CHS828			Smiles	C1=CC(=CC=C1OCCCCCCN=C(NC#N)NC2=CC=NC=C2)Cl

Solubilidad

In vitro
Lote:

DMSO : 74 mg/mL (198.99 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:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	3.700mg/ml (9.95mM)	Taking the 1 mL working solution as an example, add 50 μL of 74 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	0.520mg/ml (1.40mM)	Taking the 1 mL working solution as an example, add 50 μL of 10.4 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

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)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

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

Targets/IC₅₀/Ki	NAMPT <25 nM NAMPT 120 nM(Kd)
In vitro	GMX1778 induce la depleción de NAD+ a través de la inhibición de la biosíntesis de NAD+, seguido de la depleción de ATP y, en última instancia, resulta en la muerte celular. Este compuesto induce la muerte celular programada con características apoptóticas. Suprime la actividad del factor nuclear kappa B en células cancerosas mediante la regulación a la baja de la actividad de IKK (IC50=8 nM).
Ensayo de quinasa	Ensayo NAMPT de enzima acoplada in vitro
Ensayo de quinasa	La actividad de la NAMPT recombinante se evalúa utilizando un ensayo de enzima acoplada basado en la cuantificación de NAD+. Las reacciones se realizan a temperatura ambiente durante 180 min utilizando mezclas que consisten en 50 mM HEPES (pH 7,4), 50 mM KCl, 5 mM MgCl₂, 0,5 mM β-mercaptoetanol, 0,005% de albúmina de suero bovino, 1% de DMSO, 2,0 U/ml de lactato deshidrogenasa, 4 mM de L-lactato de sodio, 0,4 U/ml de diaforasa, 6 μM de sal sódica de resazurina, 0,4 mM de PRPP, 3,0 nM de NMNAT1, 125 μM de ATP, 50 μM de NM y 2 a 5 μM de NAMPT recombinante. La fluorescencia se mide con un lector de placas Tecan Safire (longitud de onda de excitación, 560 nm; longitud de onda de emisión, 590 nm). Los valores de Ki se calculan utilizando el software Graphpad Prism 4.0 y la ecuación de Cheng-Prusoff.
In vivo	GMX1778 (250 mg/kg, p.o.) muestra una marcada actividad antitumoral contra tres tumores neuroendocrinos humanos diferentes, carcinoide de intestino medio (GOT1), carcinoide pancreático (BON) y carcinoma medular de tiroides (GOT2), trasplantados en ratones desnudos.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/19703994/ [2] https://pubmed.ncbi.nlm.nih.gov/11205250/ [3] https://pubmed.ncbi.nlm.nih.gov/15197771/ [4] https://pubmed.ncbi.nlm.nih.gov/16508338/

Soporte técnico

Instrucciones de manipulación

Tel: +1-832-582-8158 Ext:3

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Preguntas frecuentes

Pregunta 1:
Could you please suggest me the suitable formulation of it for in vivo study?

Respuesta:
It can be dissolved in 1%CMC-Na (suspension) for oral administration.

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