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| 25mg |
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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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| Additional Infomation |
FK-866 is a member of benzamides and a N-acylpiperidine.
Daporinad has been used in trials studying the treatment of Melanoma, Cutaneous T-cell Lymphoma, and B-cell Chronic Lymphocytic Leukemia. Daporinad is a small molecule with potential antineoplastic and antiangiogenic activities. Daporinad binds to and inhibits nicotinamide phosphoribosyltransferase (NMPRTase), inhibiting 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, this agent may inhibit tumor cell production of vascular endothelial growth factor (VEGF), resulting in the inhibition of tumor angiogenesis. The coenzyme NAD+ plays an essential role in cellular redox reactions, including the redox reaction linking the citric acid cycle and oxidative phosphorylation. |
| Molecular Formula |
C24H29N3O2
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| Molecular Weight |
391.51
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| Exact Mass |
391.225
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| CAS # |
658084-64-1
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| Related CAS # |
658084-64-1;201034-75-5;1785666-54-7 (HCl);1198425-96-5 (deleted);
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| PubChem CID |
6914657
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| Appearance |
White to light yellow solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
629.9±51.0 °C at 760 mmHg
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| Flash Point |
334.8±30.4 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.589
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| LogP |
2.45
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
29
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| Complexity |
534
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CN(CCC1CCCCNC(=O)/C=C/C2=CN=CC=C2)C(=O)C3=CC=CC=C3
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| InChi Key |
KPBNHDGDUADAGP-VAWYXSNFSA-N
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| InChi Code |
InChI=1S/C24H29N3O2/c28-23(12-11-21-8-6-15-25-19-21)26-16-5-4-7-20-13-17-27(18-14-20)24(29)22-9-2-1-3-10-22/h1-3,6,8-12,15,19-20H,4-5,7,13-14,16-18H2,(H,26,28)/b12-11+
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| Chemical Name |
(E)-N-[4-(1-benzoylpiperidin-4-yl)butyl]-3-pyridin-3-ylprop-2-enamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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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) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 45% Propylene glycol (dissolve first)+5% Tween 80+ddH2O: 15mg/mL Solubility in Formulation 5: 4 mg/mL (10.22 mM) in 20% SBE-β-CD in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. |
| 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00435084 | Completed | Drug: APO866 | B-cell Chronic Lymphocytic Leukemia | Valerio Therapeutics | February 2007 | Phase 1 Phase 2 |
| NCT00432107 | Completed | Drug: APO866 | Melanoma | Valerio Therapeutics | July 2006 | Phase 2 |
| NCT00431912 | Completed | Drug: APO866 | Cutaneous T-cell Lymphoma | Valerio Therapeutics | February 2007 | Phase 2 |
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