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

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Kwaliteitscontrole

Batch: Zuiverheid: 99.99%

99.99

Producten Vaak Samen Gebruikt Met 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.

Gerelateerde doelwitten	Dehydrogenase HSP P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism Drug Metabolite
Overige Transferase Inhibitoren	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

Celkweek, behandeling & werkconcentratie

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

Chemische informatie, Opslag en Stabiliteit

Moleculair gewicht	391.51	Formule	C₂₄H₂₉N₃O₂	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	658084-64-1	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	APO866			Smiles	C1CN(CCC1CCCCNC(=O)C=CC2=CN=CC=C2)C(=O)C3=CC=CC=C3

Oplosbaarheid

In vitro
Batch:

DMSO : 78 mg/mL (199.22 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 78 mg/mL

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

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	NMPRTase (Cell-free assay) 0.4 nM(Ki)
In vitro	FK866 (Daporinad) induceert in lage concentraties van 0,09-27 nM dosisafhankelijke cytotoxiciteit in 41 hematologische kwaadaardige cellen, waaronder acute myeloïde leukemie [AML], acute lymfoblastische leukemie [ALL], mantelcellymfoom [MCL], chronische lymfoblastische leukemie [CLL] en T-cellymfoom. In concentraties van 0-10 nM induceert deze verbinding celdood, een effect dat onafhankelijk is van caspase-activering, maar geassocieerd is met depolarisatie van de mitochondriale membraan. Het induceert ook dosisafhankelijk de uitputting van intracellulaire NAD- en ATP-gehaltes en celdood in verschillende hematologische kankercellen in concentraties van 0-10 nM. In een concentratie van 10 nM remt het de door PBEF geïnduceerde secretie van MMP-3, CCL2 en CXCL8 in HFFF2-cellen.
In vivo	FK866 (Daporinad), tweemaal daags gedurende 4 dagen intraperitoneaal toegediend in een dosis van 20 mg/kg, wekelijks herhaald gedurende 3 weken, voorkomt en onderdrukt tumorgroei in C.B.-17 SCID-muizenxenograftmodellen van humane AML, lymfoblastisch lymfoom en leukemie. In een dosis van 0,12 mg/kg/uur voorkomt deze verbinding gewrichtsvernietiging en leukocyteninfiltratie door remming van PBEF bij muizen met CIA.
Referenties	[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/

Toepassingen

Methoden	Biomarkers	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

Informatie klinische proef

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Rekrutering	Aandoeningen	Sponsor/Medewerkers	Startdatum	Fasen
NCT00435084	Completed	B-cell Chronic Lymphocytic Leukemia	Valerio Therapeutics	February 2007	Phase 1\|Phase 2

Technische ondersteuning

Gebruiksaanwijzing

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

Als u nog andere vragen heeft, kunt u een bericht achterlaten.

Veelgestelde vragen

Vraag 1:
We are considering the use of it for in vivo injections. Any suggestions for the formula?

Antwoord:
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.

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FK866 (Daporinad) NAMPT-remmer

Chemische structuur

Moleculair gewicht: 391.51