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Synonyms: GNE617
| Description | GNE-617, a specific NAMPT inhibitor(IC50=5 nM), shows potency in xenograft models of cancer. |
| Targets & IC50 | NAMPT:5 nM |
| In vitro | In A549 cell, GNE-617 inhibits NAMPT (IC50=18.9 nM) . |
| In vivo | In rat studies, GNE-617 hydrochloride (QD) and GNE-875 (BID) demonstrated greater retinal toxicity at comparable exposures and durations of dosing than did GMX-1778 (BID). The efficacy studies in mice, which evaluated GNE-617, GNE-618, and GMX-1778, also opportunistically investigated retinal toxicity. NAMPTi-induced retinal toxicity was identified in cases involving GNE-617 and GMX-1778. However, varying study durations for GNE-617 and GMX-1778 preclude a direct comparison of their retinal toxicity profiles. |
| Synonyms | GNE617 |
| Kinase Assay | For RNA interference (RNAi), A549 cells are plated at 1,500 cells per well in 96-well plates, allowed to adhere for 24 hours, and transfected with 25 nM siRNA oligonucleotide using Dharmafect 4. Transfected cells are treated with the indicated concentrations of GNE-617 (0.1, 1 , 10 , 100 , and 1000 nM) for 72 hours and viability is evaluated with CellTiter-Glo. Lysates for detection of NAPRT1 protein are collected 72 hours after transfection of 1 million A549 cells in 10 cm dishes. For NAPRT1 re-expression, RERF-LC-MS cells are transfected with pCMV6-AC.NAPRT1 and empty vector pCMV6-AC using Amaxa Nucleofector technology and selected with Geneticin |
| Cell Research | GNE-617 is dissolved in DMSO and stored, and then diluted with appropriate media before use.Cells are grown in RPMI-1640 medium supplemented with 10% FBS and 2 mM glutamine and passaged not more than 20 times after thawing. To determine the IC50 values and nicotinic acid rescue status, cells are treated with nine point dose titrations of GNE-617 with or without 10 μM nicotinic acid. At 96 hours post-drug addition, the GNE-617-treated cells are evaluated using CyQUANT Direct Cell Proliferation Assay followed by CellTiter-Glo Luminescent Cell Viability Assay quantified with a Wallac EnVision 2104 Multilabel Reader. IC50 values are calculated using XLfit 5.1. To examine the protein level, cells are lysed in ice-cold radioimmunoprecipitation assay buffer, run on SDS-PAGE (4%-12% Bis-Tris), and evaluated by Western blotting using antibodies directed against NAPRT1 and β-actin |
| Animal Research | Male na?ve Sprague Dawley rats are administered once daily via oral gavage with GNE-617( 30?mg/kg), formulated as a solution in the vehicle of 60% polyethylene glycol (PEG 400)/10% ethanol/30% 5% dextrose in water (D5W) . |
| Molecular Weight | 427.42 |
| Formula | C21H15F2N3O3S |
| Cas No. | 1362154-70-8 |
| Smiles | Fc1cc(F)cc(c1)S(=O)(=O)c1ccc(CNC(=O)c2ccc3nccn3c2)cc1 |
| Relative Density. | 1.42 g/cm3 (Predicted) |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year Shipping with blue ice/Shipping at ambient temperature. | ||||||||||||||||||||||||||||||
| Solubility Information | DMSO: 25 mg/mL (58.49 mM), Sonication is recommended.  | ||||||||||||||||||||||||||||||
| In Vivo Formulation | 10% DMSO+40% PEG300+5% Tween 80+45% Saline: 1 mg/mL (2.34 mM), Sonication is recommended. Please add the solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately. The formulation provided above is for reference purposes only. In vivo formulations may vary and should be modified based on specific experimental conditions. | ||||||||||||||||||||||||||||||
Solution Preparation Table | |||||||||||||||||||||||||||||||
DMSO
Note : The dilution table applies only to solid products. For liquid products, please calculate the stock solution based on the stated concentration and/or density. | |||||||||||||||||||||||||||||||
For example, if the intended dosage is 10 mg/kg for animals weighing 20 g , with a dosing volume of 100 μL per animal, and a total of 10 animals are to be administered, using a formulation of 
10% DMSO+ 40% PEG300+ 5% Tween 80+ 45% Saline/PBS/ddH2O , the resulting working solution concentration would be 2 mg/mL.Dissolve 2 mg of the compound in 100 μL DMSO to obtain a stock solution at a concentration of 20 mg/mL . If the required concentration exceeds the compound's known solubility, please contact us for technical support before proceeding.
1) Add 100 μL of the DMSO stock solution to 400 µL PEG300 and mix thoroughly until the solution becomes clear.
2) Add 50 µL Tween 80 and mix well until fully clarified.
3) Add 450 µL Saline,PBS or ddH2O and mix thoroughly until a homogeneous solution is obtained.
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