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FK866 (APO866, Daporinad)

Names

[ CAS No. ]:
658084-64-1

[ Name ]:
FK866 (APO866, Daporinad)

[Synonym ]:
2gvj
Daporinad
2-Propenamide, N-[4-(1-benzoyl-4-piperidinyl)butyl]-3-(3-pyridinyl)-, (2E)-
(2E)-N-[4-(1-Benzoyl-4-piperidinyl)butyl]-3-(3-pyridinyl)acrylamide
FK866 (APO866, Daporinad)
FK 866
FK866 (APO866,Daporinad)
APO866
(E)-N-[4-(1-BENZOYL-PIPERIDIN-4-YL)-BUTYL]-3-PYRIDIN-3-YL-ACRYLAMIDE
FK866

Biological Activity

[Description]:

FK866 is an effective inhibitor of nicotinamide phosphoribosyltransferase (NMPRTase) with an IC50 of 0.09 nM.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy
Signaling Pathways >> Metabolic Enzyme/Protease >> Nampt
Research Areas >> Cancer

[Target]

IC50: 0.09 nM (NMPRTase)


[In Vitro]

Nampt inhibition with FK866 induces significant NAD+ intracellular reduction and selectively kills MM cells. FK866-induced cell death is associated with inhibition of Nampt activity, rather than protein expression, and higher NAD+ baseline levels in MM cells than normal PBMCs confer FK866 sensitivity. FK866 abrogates the survival advantage conferred by the bone marrow microenvironment[1]. FK866 prevents the [Ca2+]i increase induced by different mitogens and reduces the Ca2+ content of TG-responsive Ca2+ stores in Jurkat and in activated PBLs. FK866 reduces the Ca2+ content of TG-responsive Ca2+ stores in Jurkat cells but not in Bcl2-Jurkat cells[2]. Inhibition of NAMPT by FK866, or inhibition of SIRT by nicotinamide decreases proliferation and triggered death of 293T cells involving the p53 acetylation pathway[3].

[In Vivo]

FK866 (30 mg/kg, i.p.) decreases the tumor burden in CB17-SCID mice, and the tumor tissue demonstrates a significant decrease in ERK phosphorylation and proteolytic cleavage of LC3[1].

[Cell Assay]

MM1S cells (2×104 cells/well) are cultured for 72 and 96 hours in BMSC-coated 96-well plates in the presence or absence of drug. DNA synthesis is measured by (3H)-thymidine uptake, with (3H)-thymidine added (0.5 μCi/well) during the last 8 hours of cultures.

[Animal admin]

CB17-SCID mice (28-35 days old) are irradiated (200 cGy), and then inoculated subcutaneously in the right flank with 3×106 MM1S cells in 100 μL RPMI 1640. After detection of tumor (2 weeks after the injection), 7 mice are treated intraperitoneally with either vehicle or FK866 (30 mg/kg body weight) twice a day for 4 days, repeated weekly over 3 weeks. Caliper measurements of the longest perpendicular tumor diameters are performed twice a week to estimate the tumor volume using the following formula: length×width2×0.5. Tumor growth inhibition (TGI) is calculated. Animals are killed when tumors reach 2 cm3 or the mice appear moribund. Survival is evaluated from the first day of treatment until death.

[References]

[1]. Cea M, et al. Targeting NAD+ salvage pathway induces autophagy in multiple myeloma cells via mTORC1 and extracellular signal-regulated kinase (ERK1/2) inhibition. Blood. 2012 Oct 25;120(17):3519-29.

[2]. Magnone M, et al. NAD+ levels control Ca2+ store replenishment and mitogen-induced increase of cytosolic Ca2+ by Cyclic ADP-ribose-dependent TRPM2 channel gating in human T lymphocytes. J Biol Chem. 2012 Jun 15;287(25):21067-81.

[3]. Thakur BK, et al. Inhibition of NAMPT pathway by FK866 activates the function of p53 in HEK293T cells. Biochem Biophys Res Commun. 2012 Aug 3;424(3):371-7.


[Related Small Molecules]

P7C3 | STF 118804 | GMX1778 | KPT-9274 | GNE-617 | Nampt-IN-1 | CB 300919 | CB30865

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
629.9±51.0 °C at 760 mmHg

[ Molecular Formula ]:
C24H29N3O2

[ Molecular Weight ]:
391.506

[ Flash Point ]:
334.8±30.4 °C

[ Exact Mass ]:
391.225983

[ PSA ]:
62.30000

[ LogP ]:
2.45

[ Appearance of Characters ]:
white to beige

[ Vapour Pressure ]:
0.0±1.8 mmHg at 25°C

[ Index of Refraction ]:
1.589

[ Storage condition ]:
?20°C

[ Water Solubility ]:
DMSO: soluble10mg/mL, clear

Safety Information

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
22

Related Compounds