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GMX1778 NAMPT remmer

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

Cat.Nr.S8117

GMX1778 is een potente en specifieke remmer van nicotinamide phosphoribosyltransferase (NAMPT) met een IC50 en K_d van respectievelijk < 25 nM en 120 nM. Deze verbinding induceert geprogrammeerde celdood met apoptotische kenmerken. Fase 1.

Chemische structuur

Moleculair gewicht: 371.86

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Kwaliteitscontrole

Batch: S811701 DMSO]74 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Zuiverheid: 99.82%

Genoemd in Nature Medicine voor zijn topkwaliteit
COA
NMR
HPLC
SDS
Datasheet

99.82

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

Celkweek, behandeling & werkconcentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	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
Klik om meer experimentele gegevens over de cellijn te bekijken

Chemische informatie, Opslag en Stabiliteit

Moleculair gewicht	371.86	Formule	C₁₉H₂₂ClN₅O	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	200484-11-3	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	CHS828			Smiles	C1=CC(=CC=C1OCCCCCCN=C(NC#N)NC2=CC=NC=C2)Cl

Oplosbaarheid

In vitro
Batch:

DMSO : 74 mg/mL (198.99 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Moleculair gewicht
=	×	×

Verdunningscalculator Moleculair gewicht calculator

In vivo Batch:
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 Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	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 Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	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.

In vivo Formuleringscalculator (Heldere oplossing)

Stap 1: Voer de onderstaande informatie in (Aanbevolen: Een extra dier voor het geval van verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in het gedeelte Oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-mastervloeistof: mg geneesmiddel vooraf opgelost in μL DMSO ( Concentratie mastervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de partij geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toeμL PEG300, mengen en helder maken, voeg vervolgens toeμL Tween 80, mengen en helder maken, voeg vervolgens toe μL ddH₂O, mengen en helder maken.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toe μL Maïsolie, mengen en helder maken.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysische methoden zoals vortexen, echografie of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Targets/IC₅₀/Ki	NAMPT <25 nM NAMPT 120 nM(Kd)
In vitro	GMX1778 induceert NAD+ uitputting door remming van NAD+ biosynthese, gevolgd door ATP uitputting en resulteert uiteindelijk in celdood. Deze verbinding induceert geprogrammeerde celdood met apoptotische kenmerken. Het onderdrukt de nucleaire factor-kappa B activiteit in kankercellen door neerwaartse regulatie van IKK activiteit (IC50=8 nM).
Kinase Assay	In vitro gekoppelde-enzym NAMPT assay
Kinase Assay	Recombinant NAMPT activiteit wordt beoordeeld met behulp van een gekoppelde-enzym assay gebaseerd op de kwantificering van NAD+. Reacties worden uitgevoerd bij kamertemperatuur gedurende 180 min met mengsels bestaande uit 50 mM HEPES (pH 7.4), 50 mM KCl, 5 mM MgCl₂, 0.5 mM β-mercaptoethanol, 0.005% bovine serum albumine, 1% DMSO, 2.0 U/ml lactaatdehydrogenase, 4 mM natrium-L-lactaat, 0.4 U/ml diaforase, 6 μM resazurine natriumzout, 0.4 mM PRPP, 3.0 nM NMNAT1, 125 μM ATP, 50 μM NM, en 2 tot 5 μM recombinant NAMPT. Fluorescentie wordt gemeten met een Tecan Safire plaatlezer (excitatiegolflengte, 560 nm; emissiegolflengte, 590 nm). Ki-waarden worden berekend met Graphpad Prism 4.0 software en de Cheng-Prusoff vergelijking.
In vivo	GMX1778 (250 mg/kg, p.o.) toont een duidelijke antitumorale activiteit tegen drie verschillende menselijke neuro-endocriene tumoren, middendarmcarcinoïd (GOT1), pancreatisch carcinoïd (BON), en medullair schildkliercarcinoom (GOT2), getransplanteerd in naakte muizen.
Referenties	[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/

Technische ondersteuning

Gebruiksaanwijzing

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

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Veelgestelde vragen

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

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

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