Home Metabolism Transferase inhibitor FK866 (Daporinad)

solo para uso en investigación

FK866 (Daporinad) Nampt inhibitor

Cat. No.: S2799

FK866 (Daporinad) effectively inhibits nicotinamide phosphoribosyltransferase (NMPRTase; Nampt) with IC50 of 0.09 nM in a cell-free assay. This compound triggers autophagy. Phase 1/2.
FK866 (Daporinad) Transferase inhibitor Chemical Structure

Estructura química

Peso molecular: 391.51

Saltar a

Control de calidad (Quality Control)

Lote: Pureza: 99.99%
99.99

Productos que se suelen utilizar junto con 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.

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Líneas celulares Tipo de ensayo Concentración Tiempo de incubación Formulación Descripción de la actividad 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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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular 391.51 Fórmula

C24H29N3O2

 Almacenamiento (Desde la fecha de recepción)
Nº CAS 658084-64-1 Descargar SDF Almacenamiento de soluciones madre

Sinónimos APO866 Smiles C1CN(CCC1CCCCNC(=O)C=CC2=CN=CC=C2)C(=O)C3=CC=CC=C3

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 78 mg/mL (199.22 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 78 mg/mL

Water : Insoluble

Calculadora de Molaridad

Masa Concentración Volumen Peso molecular
Calculadora de Dilución Calculadora de Peso Molecular

In vivo
Lote:

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

mg/kg g μL

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH2O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción (Mechanism of Action)

Targets/IC50/Ki
NMPRTase
(Cell-free assay)
0.4 nM(Ki)
In vitro
FK866 (Daporinad) at low concentrations ranging from 0.09-27 nM induces dose-dependent cytotoxicity in 41 hematologic malignant cells including acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], mantle cell lymphoma [MCL], chronic lymphocytic leukemia [CLL], and T-cell lymphoma. At concentrations ranging from 0-10 nM, this compound induces cell death, an effect independent of caspase activation but associated with depolarization of mitochondrial membrane. It also dose-dependently induces depletion of intracellular NAD and ATP contents and cell death in various hematologic cancer cells at concentrations ranging from 0-10 nM. At a concentration of 10 nM, it inhibits PBEF-induced secretion of MMP-3, CCL2, and CXCL8 in HFFF2 cells.
In vivo
FK866 (Daporinad) administered intraperitoneally at a dose of 20 mg/kg twice a day for 4 days, repeated weekly over 3 weeks, prevents and abrogates tumor growth in C.B.-17 SCID mice xenograft models of human AML, lymphoblastic lymphoma, and leukemia. At a dose of 0.12 mg/kg/hour, this compound prevents joint destruction and leukocyte infiltration through inhibition of PBEF in mice with CIA.
Referencias
  • [4] https://pubmed.ncbi.nlm.nih.gov/20696207/
  • [5] https://pubmed.ncbi.nlm.nih.gov/14612543/

Aplicaciones (Applications)

Métodos Biomarcadores Imágenes PMID
Western blot SIRT1 p-AMPK / AMPK / p-EIF2A / EIF2A / p-4EBP1 / 4EBP1 AKT / pAKT(Ser-473) / mTOR / p-mTOR(Ser-2448)
S2799-WB1
29905535
Immunofluorescence pMLKL phGSK3β ph-β-catenin
S2799-IF1
29996103
Growth inhibition assay Cell viability
S2799-viability1
27462772

Información del ensayo clínico (Clinical Trial Information)

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT Reclutamiento Condiciones Patrocinador/Colaboradores Fecha de inicio Fases
NCT00435084 Completed
B-cell Chronic Lymphocytic Leukemia
Valerio Therapeutics
 February 2007 Phase 1|Phase 2

Preguntas frecuentes (Frequently Asked Questions)

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

Respuesta:
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.