FK866 (APO866)
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.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 391.51 |
| Cas No. | 658084-64-1 |
| Formula | C24H29N3O2 |
| 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 |
| SDF | Download SDF |
| Canonical SMILES | C1CN(CCC1CCCCNC(=O)C=CC2=CN=CC=C2)C(=O)C3=CC=CC=C3 |
| Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request |
| General tips | For 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. |
| Cell experiment [1]: | |
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Cell lines |
41 hematologic malignant cell lines |
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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. |
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Reaction Conditions |
0 ~ 10 nM; 72 or 96 hrs |
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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]: | |
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Animal models |
C.B.-17 SCID mice xenograft models of human AML, lymphoblastic lymphoma and leukemia |
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Dosage form |
20 mg/kg; i.p.; twice daily for 4 days, repeated weekly 3 times |
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Applications |
In C.B.-17 SCID mice xenograft models of human AML, lymphoblastic lymphoma and leukemia, APO866 prevented and abrogated tumor growth. |
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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. |
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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. | |
| 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 & MSDS
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Chemical structure
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