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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Other Sizes |
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Purity: ≥98%
Daporinad (APO866; FK-866; APO-866; K 22.175) is a novel and potent inhibitor of nicotinamide phosphoribosyltransferase (NMPRTase) with potential antitumor and antiangiogenic activity. It inhibits NMPRTase with an IC50 of 0.09 nM in a cell-free assay. FK866 acts by binding to and inhibiting nicotinamide phosphoribosyltransferase (NMPRTase), thus blocking the biosynthesis of nicotinamide adenine dinucleotide (NAD+) from niacinamide (vitamin B3), which may deplete energy reserves in metabolically active tumor cells and induce tumor cell apoptosis. In addition, Daporinad may inhibit the production of vascular endothelial growth factor (VEGF) in tumor cells, leading to the inhibition of tumor angiogenesis.
ln Vitro |
By selectively killing MM cells, Nampt inhibition with (E)-Daporinad (FK866) causes a large intracellular decrease in NAD+. Higher baseline NAD+ levels in MM cells than in normal PBMCs give (E)-Daporinad (FK866) sensitivity. (E)-Daporinad (FK866)-induced cell death is related with inhibition of Nampt activity, rather than protein expression. The bone marrow microenvironment's survival advantage is eliminated by (E)-Daporinad (FK866)[1]. (E)-Daporinad (FK866) lowers the Ca2+ content of TG-responsive Ca2+ stores in Jurkat and activated PBLs and inhibits the [Ca2+]i rise brought on by various mitogens. The Ca2+ content of TG-responsive Ca2+ stores in Jurkat cells is decreased by (E)-Daporinad (FK866), but not in Bcl2-Jurkat cells[2]. Using the p53 acetylation route, suppression of NAMPT by (E)-Daporinad (FK866) or inhibition of SIRT by nicotinamide reduces proliferation and causes death of 293T cells[3].
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ln Vivo |
In CB17-SCID mice, (E)-Daporinad (FK866) (30 mg/kg, ip) reduces the tumor burden and significantly reduces ERK phosphorylation and proteolytic cleavage of LC3 in the tumor tissue[1].
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Animal Protocol |
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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 |
Molecular Formula |
C24H29N3O2
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Molecular Weight |
391.51
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CAS # |
658084-64-1
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SMILES |
O=C(C1C([H])=C([H])C([H])=C([H])C=1[H])N1C([H])([H])C([H])([H])C([H])(C([H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(/C(/[H])=C(\[H])/C2=C([H])N=C([H])C([H])=C2[H])=O)C([H])([H])C1([H])[H]
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Synonyms |
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.5542 mL | 12.7711 mL | 25.5421 mL | |
5 mM | 0.5108 mL | 2.5542 mL | 5.1084 mL | |
10 mM | 0.2554 mL | 1.2771 mL | 2.5542 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.