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GMX1778 NAMPT inibitore

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

N. Cat.S8117

GMX1778 è un potente e specifico inibitore della nicotinamide fosforibosiltransferasi (NAMPT) con IC50 e K_d rispettivamente di < 25 nM e 120 nM. Questo composto induce la morte cellulare programmata con caratteristiche apoptotiche. Fase 1.

GMX1778 NAMPT inibitore Chemical Structure

Struttura chimica

Peso molecolare: 371.86

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Controllo Qualità

Lotto: S811701 DMSO]74 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purezza: 99.82%

Citato in Nature Medicine per la sua qualità superiore
COA
NMR
HPLC
SDS
Scheda tecnica

99.82

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

Coltura cellulare, trattamento e concentrazione di lavoro

Linee cellulari	Tipo di saggio	Concentrazione	Tempo di incubazione	Descrizione dellattività	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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Informazioni chimiche, conservazione e stabilità

Peso molecolare	371.86	Formula	C₁₉H₂₂ClN₅O	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	200484-11-3	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	CHS828			Smiles	C1=CC(=CC=C1OCCCCCCN=C(NC#N)NC2=CC=NC=C2)Cl

Solubilità

In vitro
Lotto:

DMSO : 74 mg/mL (198.99 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Water : Insoluble

Ethanol : Insoluble

Calcolatore di Molarità

Massa	Concentrazione	Volume	Peso molecolare
=	×	×

Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo Lotto:
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 Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	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 Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	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.

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante lesperimento)

Dosaggio: mg/kg Peso medio degli animali: g Volume di dosaggio per animale:μL Numero di animali:

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non cè una formulazione in vivo nella sezione Solubilità.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH₂O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nellaggiunta precedente, sia una soluzione limpida prima di procedere allaggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno dacqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo dazione

Targets/IC₅₀/Ki	NAMPT <25 nM NAMPT 120 nM(Kd)
In vitro	GMX1778 induce la deplezione di NAD+ attraverso l'inibizione della biosintesi di NAD+, seguita dalla deplezione di ATP e, in ultima analisi, dalla morte cellulare. Questo composto induce la morte cellulare programmata con caratteristiche apoptotiche. Sopprime l'attività del fattore nucleare kappa B nelle cellule tumorali attraverso la down-regolazione dell'attività di IKK (IC50=8 nM).
Saggio chinasico	Saggio NAMPT a enzima accoppiato in vitro
Saggio chinasico	L'attività della NAMPT ricombinante viene valutata utilizzando un saggio enzimatico accoppiato basato sulla quantificazione del NAD+. Le reazioni vengono eseguite a temperatura ambiente per 180 minuti utilizzando miscele costituite da 50 mM HEPES (pH 7,4), 50 mM KCl, 5 mM MgCl₂, 0,5 mM β-mercaptoetanolo, 0,005% di albumina sierica bovina, 1% di DMSO, 2,0 U/ml di lattato deidrogenasi, 4 mM di L-lattato di sodio, 0,4 U/ml di diaforasi, 6 μM di sale sodico di resazurina, 0,4 mM di PRPP, 3,0 nM di NMNAT1, 125 μM di ATP, 50 μM di NM e da 2 a 5 μM di NAMPT ricombinante. La fluorescenza viene misurata con un lettore di piastre Tecan Safire (lunghezza d'onda di eccitazione, 560 nm; lunghezza d'onda di emissione, 590 nm). I valori di Ki vengono calcolati utilizzando il software Graphpad Prism 4.0 e l'equazione di Cheng-Prusoff.
In vivo	GMX1778 (250 mg/kg, p.o.) mostra una marcata attività antitumorale contro tre diversi tumori neuroendocrini umani, carcinoide del mesentere (GOT1), carcinoide pancreatico (BON) e carcinoma midollare della tiroide (GOT2), trapiantati in topi nudi.
Riferimenti	[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/

Supporto tecnico

Istruzioni per la manipolazione

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

Per qualsiasi altra domanda, si prega di lasciare un messaggio.

Domande Frequenti

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

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

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