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FK866 (APO866)

In stock
Catalog No.
A4381
NAMPT inhibitor,non-competitive, highly specific
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$65.00
In stock
5mg
$60.00
In stock
10mg
$110.00
In stock
25mg
$250.00
In stock
50mg
$390.00
In stock

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Background

FK866 is an inhibitor of nicotinamide phosphoribosyltransferase (NMPRTase) with IC50 values ranging between 0.09nM and 27.2nM [1].

NAD plays a vital role in numerous biochemical and biologic processes. Targeting NAD synthesis is thought to be a selective manner to kill cancer cells since cancer cells have a higher rate of NAD turnover compared with normal cells. In the in vitro MTT assay using a panel of 41 human hematologic cancer

cell lines, most cancer cells are sensitive to low concentrations of FK866. Among these cancer cells, AML cells are most sensitive. FK866 is shown selective to human hematologic malignant cells and the normal human HPCs are resistant to FK866 treatment. It is found that FK866 induces cell death in a caspase-independent pathway but in a dose-dependent manner to induce mitochondrial membrane depolarization. Additionally, FK866 induces cell autophagy dependenting on de novo protein synthesis. FK866 also reduces ATP levels in ML-2 cells due to the inhibition of NAD synthesis. The antitumor efficacy of FK866 is also shown in the in vivo models. FK866 significantly prevents tumor growth both in mice xenografted subcutaneously with AML-M4 and Namalwa cells. Furthermore, FK866 clears tumor cells to below detectable levels and results in 80% survival for a long-term [1].

References:
[1] Nahimana A, Attinger A, Aubry D, Greaney P, Ireson C, Thougaard AV, Tjørnelund J, Dawson KM, Dupuis M, Duchosal MA. The NAD biosynthesis inhibitor APO866 has potent antitumor activity against hematologic malignancies. Blood. 2009 Apr 2;113(14):3276-86.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt391.51
Cas No.658084-64-1
FormulaC24H29N3O2
Solubility≥19.6mg/mL in DMSO, ≥49.6 mg/mL in EtOH, <2.41 mg/mL in H2O
Chemical Name(E)-N-[4-(1-benzoylpiperidin-4-yl)butyl]-3-pyridin-3-ylprop-2-enamide
SDFDownload SDF
Canonical SMILESC1CN(CCC1CCCCNC(=O)C=CC2=CN=CC=C2)C(=O)C3=CC=CC=C3
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Protocol

Cell experiment [1]:

Cell lines

41 hematologic malignant cell lines

Preparation method

The solubility of this compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months.

Reaction Conditions

0 ~ 10 nM; 72 or 96 hrs

Applications

In various hematologic cancer cells, APO866 (0 ~ 10 nM) dose-dependently induced depletion of intracellular NAD and ATP contents and cell death.

Animal experiment [1]:

Animal models

C.B.-17 SCID mice xenograft models of human AML, lymphoblastic lymphoma and leukemia

Dosage form

20 mg/kg; i.p.; twice daily for 4 days, repeated weekly 3 times

Applications

In C.B.-17 SCID mice xenograft models of human AML, lymphoblastic lymphoma and leukemia, APO866 prevented and abrogated tumor growth.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Nahimana A, Attinger A, Aubry D, Greaney P, Ireson C, Thougaard AV, Tj?rnelund J, Dawson KM, Dupuis M, Duchosal MA. The NAD biosynthesis inhibitor APO866 has potent antitumor activity against hematologic malignancies. Blood. 2009 Apr 2;113(14):3276-86.

Biological Activity

Description FK866 is a highly specific non-competitive inhibitor of nicotinamide phosphoribosyltransferase (NAMPT) with Ki value of 0.4 nM.
Targets NAMPT          
IC50 0.4 nM (Ki)          

Quality Control

Chemical structure

FK866 (APO866)

Related Biological Data

FK866 (APO866)