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GMX1778 NAMPT inhibiteur

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

Réf. CatalogueS8117

GMX1778 est un inhibiteur puissant et spécifique de la nicotinamide phosphoribosyltransférase (NAMPT) avec une IC50 et une K_d de < 25 nM et 120 nM, respectivement. Ce composé induit la mort cellulaire programmée avec des caractéristiques apoptotiques. Phase 1.

GMX1778 NAMPT inhibiteur Chemical Structure

Structure chimique

Poids moléculaire: 371.86

Aller à

Contrôle Qualité

Lot : S811701 DMSO]74 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Pureté : 99.82%

Cité dans Nature Medicine pour sa qualité supérieure
COA
NMR
HPLC
SDS
Fiche technique

99.82

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

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires	Type dessai	Concentration	Temps dincubation	Description de lactivité	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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Informations chimiques, stockage et stabilité

Poids moléculaire	371.86	Formule	C₁₉H₂₂ClN₅O	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	200484-11-3	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	CHS828			Smiles	C1=CC(=CC=C1OCCCCCCN=C(NC#N)NC2=CC=NC=C2)Cl

Solubilité

In vitro
Lot:

DMSO : 74 mg/mL (198.99 mM)
(Le DMSO contaminé par lhumidité 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:
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 Validé par les laboratoires Selleck. Si vous avez besoin dajustements à cette formulation, contactez notre équipe commerciale pour des tests personnalisés.	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 Validé par les laboratoires Selleck. Si vous avez besoin dajustements à cette formulation, contactez notre équipe commerciale pour des tests personnalisés.	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.

Calculateur de formulation in vivo (Solution claire)

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

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre danimaux :

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter dabord sil ny 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 dabord 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 dajouter le solvant suivant.
2. Assurez-vous dajouter le(s) solvant(s) dans lordre. Vous devez vous assurer que la solution obtenue, lors de lajout précédent, est une solution claire avant de procéder à lajout 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 daction

Targets/IC₅₀/Ki	NAMPT <25 nM NAMPT 120 nM(Kd)
In vitro	GMX1778 induit un épuisement de NAD+ par inhibition de la biosynthèse de NAD+, suivi d'un épuisement d'ATP et aboutissant finalement à la mort cellulaire. Ce composé induit la mort cellulaire programmée avec des caractéristiques apoptotiques. Il supprime l'activité du facteur nucléaire kappa B dans les cellules cancéreuses par une régulation négative de l'activité IKK (IC50=8 nM).
Essai kinase	Test NAMPT à enzyme couplée in vitro
Essai kinase	L'activité de la NAMPT recombinante est évaluée à l'aide d'un test enzymatique couplé basé sur la quantification du NAD+. Les réactions sont réalisées à température ambiante pendant 180 min en utilisant des mélanges composés de 50 mM HEPES (pH 7,4), 50 mM KCl, 5 mM MgCl₂, 0,5 mM β-mercaptoéthanol, 0,005 % d'albumine de sérum bovin, 1 % de DMSO, 2,0 U/ml de lactate déshydrogénase, 4 mM de L-lactate de sodium, 0,4 U/ml de diaphorase, 6 μM de sel de sodium de résazurine, 0,4 mM de PRPP, 3,0 nM de NMNAT1, 125 μM d'ATP, 50 μM de NM et 2 à 5 μM de NAMPT recombinante. La fluorescence est mesurée avec un lecteur de plaques Tecan Safire (longueur d'onde d'excitation, 560 nm ; longueur d'onde d'émission, 590 nm). Les valeurs de Ki sont calculées à l'aide du logiciel Graphpad Prism 4.0 et de l'équation de Cheng-Prusoff.
In vivo	GMX1778 (250 mg/kg, p.o.) montre une activité antitumorale marquée contre trois tumeurs neuroendocrines humaines différentes, le carcinoïde du mésentère (GOT1), le carcinoïde pancréatique (BON) et le carcinome médullaire de la thyroïde (GOT2), transplantées chez des souris nues.
Références	[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/

Support technique

Instructions de manipulation

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

Si vous avez dautres questions, veuillez laisser un message.

Foire aux questions

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

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

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