Name: FK866 (Daporinad)
Brand: Selleck Chemicals
SKU: S2799
Rating: 5 (70 reviews)

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Contrôle Qualité

Lot : Pureté : 99.99%

99.99

Produits souvent utilisés avec FK866 (Daporinad)

Padnarsertib (KPT-9274, ATG-019)

It and KPT 9274 are NMPT inhibitors and can strongly decrease total NAD+ levels and mitochondrial respiration in M2 macrophages.

GMX1778

It and GMX1778 are iNAMPT enzymatic inhibitors that have been developed as anti-cancer treatment options.

Cibles apparentées	Dehydrogenase HSP P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism Drug Metabolite
Autre Transferase Inhibiteurs	Tunicamycin Ezatiostat AOA (Aminooxyacetic acid) hemihydrochloride GGTI 298 TFA salt OSMI-4 2-Bromohexadecanoic acid (2-BP) A-922500 (DGAT-1 Inhibitor 4a) PF-04620110 OSMI-1 ERG240

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires	Type dessai	Concentration	Temps dincubation	Description de lactivité	PMID
SH-SY5Y	Cytotoxicity assay			Cytotoxicity against human SH-SY5Y cells assessed as reduction of total cellular NAD(P) level, IC50 = 0.0005 μM.	19961183
SH-SY5Y	Cytotoxicity assay		48 hrs	Cytotoxicity against human SH-SY5Y cells assessed as cell viability after 48 hrs by MTT assay, IC50 = 0.0017 μM.	19961183
HT1080	Cytotoxicity assay		6 days	Cytotoxicity against human HT1080 cells after 6 days by SRB assay, IC50 = 0.16 μM.	21330015
A549	Cytotoxicity assay		6 days	Cytotoxicity against human A549 cells after 6 days by SRB assay, IC50 = 0.16 μM.	21330015
HCT116	Cytotoxicity assay		6 days	Cytotoxicity against human HCT116 cells after 6 days by SRB assay, IC50 = 0.16 μM.	21330015
SNU638	Cytotoxicity assay		6 days	Cytotoxicity against human SNU638 cells after 6 days by SRB assay, IC50 = 0.16 μM.	21330015
MCF7	Antitumor assay	10 uM	6 days	Antitumor activity against human MCF7 cells at 10 uM after 6 days by SRB assay, IC50 = 0.68 μM.	21330015
K562	Cytotoxicity assay		6 days	Cytotoxicity against human K562 cells after 6 days by SRB assay, IC50 = 20 μM.	21330015
A2780	Cytotoxicity assay		72 hrs	Cytotoxicity against human A2780 cells after 72 hrs by SRB assay, IC50 = 0.001 μM.	23617784
NYH	Cytotoxicity assay		3 weeks	Cytotoxicity against human NYH cells after 3 weeks by clonogenic survival assay, LD50 = 0.0015 μM.	23679915
K562	Cytotoxicity assay		96 hrs	Cytotoxicity against human K562 cells after 96 hrs by MTT assay, IC50 = 0.0072 μM.	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 = 0.001 μM.	23859118
NYH	Cytotoxicity assay			Cytotoxicity against human NYH cells by clonogenic assay, IC50 = 0.0015 μM.	24164086
A2780	Cytotoxicity assay		72 hrs	Cytotoxicity against human A2780 cells assessed as growth inhibition after 72 hrs by WST-1 assay, IC50 = 0.0016 μM.	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 = 0.0022 μM.	24164086
PC3	Cytotoxicity assay			Cytotoxicity against human PC3 cells by clonogenic assay, IC50 = 0.0038 μM.	24164086
A2780	Cytotoxicity assay			Cytotoxicity against human A2780 cells by clonogenic assay, IC50 = 0.0057 μM.	24164086
A431	Cytotoxicity assay			Cytotoxicity against human A431 cells by clonogenic assay, IC50 = 0.0061 μM.	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 = 0.0074 μM.	24164086
MCF7	Cytotoxicity assay			Cytotoxicity against human MCF7 cells by clonogenic assay, IC50 = 0.0084 μM.	24164086
HCT116	Cytotoxicity assay		72 hrs	Cytotoxicity against human HCT116 cells assessed as growth inhibition after 72 hrs by WST-1 assay, IC50 = 0.0109 μM.	24164086
SKOV3	Cytotoxicity assay			Cytotoxicity against human SKOV3 cells by clonogenic assay, IC50 = 0.211 μM.	24164086
HCT116	Cytotoxicity assay		72 hrs	Cytotoxicity against APO866-resistant human HCT116 cells assessed as growth inhibition after 72 hrs by WST-1 assay, IC50 = 0.946 μM.	24164086
A2780	Antiproliferative assay		72 hrs	Antiproliferative activity against human A2780 cells after 72 hrs by sulforhodamine B assay, IC50 = 0.001 μM.	24405419
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 = 0.001 μM.	27541271
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 = 0.003 μM.	27541271
SH-SY5Y	Cytotoxicity assay		56 hrs	Cytotoxicity against human SH-SY5Y cells assessed as reduction in cell viability after 56 hrs by MTT assay, EC50 = 0.0034 μM.	28165742
A2780	Cytotoxicity assay			Cytotoxicity against human A2780 cells assessed as reduction in cell viability, IC50 = 0.0042 μM.	28165742
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 = 0.0057 μM.	28610984
HepG2	Cytotoxicity assay		72 hrs	Cytotoxicity in human HepG2 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50 = 0.89 μM.	28885834
MDA-MB-231	Cytotoxicity assay		72 hrs	Cytotoxicity in human MDA-MB-231 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50 = 1.3 μM.	28885834
HCT116	Cytotoxicity assay		72 hrs	Cytotoxicity in human HCT116 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50 = 1.6 μM.	28885834
HepG2	Cytotoxicity assay		72 hrs	Cytotoxicity against human HepG2 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 0.89 μM.	29348808
HCT116	Cytotoxicity assay		72 hrs	Cytotoxicity against human HCT116 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 1.6 μM.	29348808
A549	Cytotoxicity assay		72 hrs	Cytotoxicity against human A549 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 3.7 μM.	29348808
SH-SY5Y	Autophagy assay		40 hrs	Induction of autophagy in human SH-SY5Y cells assessed as LC3/phosphotidylethanolamine coupling after 40 hrs by Western blot analysis	19961183
MCF7	Antitumor assay		6 days	Antitumor activity against human MCF7 cells after 6 days by SRB assay	21330015
MDCK	Function assay	10 uM		Apparent permeability across apical to basolateral side in dog MDCK cells at 10 uM by LC-MS/MS analysis	23859118
DU145	Cytotoxicity assay			Cytotoxicity against human DU145 cells by clonogenic assay	24164086
MCF7	Cytotoxicity assay		96 hrs	Cytotoxicity against human MCF7 cells after 96 hrs by clonogenic assay	24164086
HCT116	Function assay			Resistance factor, ratio of IC50 for APO866-resistant human HCT116 cells to IC50 for human HCT116 cells	24164086
A2780	Antiproliferative assay		72 hrs	Antiproliferative activity against human A2780 cells after 72 hrs by sulforhodamine B assay in presence of nicotinamide mononucleotide	24405419
Sf9	Function assay		30 mins	Inhibition of recombinant full length human C-terminal His/flag-tagged HDAC1 expressed in baculovirus infected Sf9 insect cells after 30 mins by fluorescence assay	29348808
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Informations chimiques, stockage et stabilité

Poids moléculaire	391.51	Formule	C₂₄H₂₉N₃O₂	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	658084-64-1	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	APO866			Smiles	C1CN(CCC1CCCCNC(=O)C=CC2=CN=CC=C2)C(=O)C3=CC=CC=C3

Solubilité

In vitro
Lot:

DMSO : 78 mg/mL (199.22 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Ethanol : 78 mg/mL

Water : 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.
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.
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.
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.	4.000mg/ml (10.22mM)	Taking the 1 mL working solution as an example, add 50 μL of 80 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.

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	NMPRTase (Cell-free assay) 0.4 nM(Ki)
In vitro	Le FK866 (Daporinad) à de faibles concentrations allant de 0,09 à 27 nM induit une cytotoxicité dose-dépendante dans 41 cellules malignes hématologiques, y compris la leucémie myéloïde aiguë [AML], la leucémie lymphoblastique aiguë [ALL], le lymphome à cellules du manteau [MCL], la leucémie lymphoïde chronique [CLL] et le lymphome à cellules T. À des concentrations allant de 0 à 10 nM, ce composé induit la mort cellulaire, un effet indépendant de l'activation des caspases mais associé à la dépolarisation de la membrane mitochondriale. Il induit également de manière dose-dépendante l'épuisement des contenus intracellulaires de NAD et d'ATP et la mort cellulaire dans diverses cellules cancéreuses hématologiques à des concentrations allant de 0 à 10 nM. À une concentration de 10 nM, il inhibe la sécrétion induite par le PBEF de MMP-3, CCL2 et CXCL8 dans les cellules HFFF2.
In vivo	Le FK866 (Daporinad) administré par voie intrapéritonéale à une dose de 20 mg/kg deux fois par jour pendant 4 jours, répété hebdomadairement sur 3 semaines, prévient et abroge la croissance tumorale dans des modèles de xénogreffe de souris C.B.-17 SCID de LAM humaine, de lymphome lymphoblastique et de leucémie. À une dose de 0,12 mg/kg/heure, ce composé prévient la destruction articulaire et l'infiltration leucocytaire par inhibition du PBEF chez les souris atteintes de CIA.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/19196867/ [2] https://pubmed.ncbi.nlm.nih.gov/21400478/ [3] https://pubmed.ncbi.nlm.nih.gov/20515945/ [4] https://pubmed.ncbi.nlm.nih.gov/20696207/ [5] https://pubmed.ncbi.nlm.nih.gov/14612543/

Applications

Méthodes	Biomarqueurs	PMID
Western blot	SIRT1 p-AMPK / AMPK / p-EIF2A / EIF2A / p-4EBP1 / 4EBP1 AKT / pAKT(Ser-473) / mTOR / p-mTOR(Ser-2448)	29905535
Immunofluorescence	pMLKL phGSK3β ph-β-catenin	29996103
Growth inhibition assay	Cell viability	27462772

Informations sur lessai clinique

(données du https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT	Recrutement	Conditions	Promoteur/Collaborateurs	Date de début	Phases
NCT00435084	Completed	B-cell Chronic Lymphocytic Leukemia	Valerio Therapeutics	February 2007	Phase 1\|Phase 2

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:
We are considering the use of it for in vivo injections. Any suggestions for the formula?

Réponse :
The recommended vehicle for in vivo study of this compound is 45% Propylene glycol (dissolve first) +5% Tween 80+ddH2O. It can be dissolved in Propylene glycol first and then diluted with water containing Tween 80. The solution is clear and suitable for injection.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

FK866 (Daporinad) inhibiteur de NAMPT

Structure chimique

Poids moléculaire: 391.51