FK866 (APO866)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
FK866 is an inhibitor of nicotinamide phosphoribosyltransferase (NMPRTase) with IC50 values ranging between 0.09 nM and 27.2 nM [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.
- 1. Huang Y, Peng Y, et al. "Nicotinamide Phosphoribosyl Transferase Controls NLRP3 Inflammasome Activity Through MAPK and NF-κB Signaling in Nucleus Pulposus Cells, as Suppressed by Melatonin." Inflammation. 2020;10.1007/s10753-019-01166-z. PMID:31900828
- 2. Shi KL, Qian JY, et al. "Atorvastatin antagonizes the visfatin-induced expression of inflammatory mediators via the upregulation of NF-κB activation in HCAECs." Oncol Lett. 2016 Aug; 12 (2): 1438-1444. PMID:27446449
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 391.51 |
| Cas No. | 658084-64-1 |
| Formula | C24H29N3O2 |
| Solubility | ≥19.6 mg/mL in DMSO, ≥49.6 mg/mL in EtOH, insoluble 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 sizes: ship with RT, or blue ice upon request. |
| General tips | For obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C 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. |
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| 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
Related Biological Data
Related Biological Data
