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Purity: ≥98%
GNE-617 hydrochloride is a specific inhibitor NAMPT (nicotinamide phosphoribosyltransferase) that inhibits the biochemical activity of NAMPT with an IC50 of 5 nM and exhibits efficacy in xenograft models of cancer. Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein with intra- and extra-cellular functions as an enzyme, cytokine, growth factor, and hormone. NAMPT is of interest for oncology, because it catalyzes the rate-limiting step in the salvage pathway to generate nicotinamide adenine dinucleotide (NAD), which is considered a universal energy- and signal-carrying molecule involved in cellular energy metabolism and many homeostatic functions. The activity of GNE-617 hydrochloride is evaluated on a panel 53 non-small cell lung cancer (NSCLC) cell lines in the presence or absence of 10 μM nicotinic acid. GNE-617 inhibits NAMPT IC50 of 18.9 nM in A549 cell.The majority of cell lines exhibit a steep dose response to GNE-617 when evaluated by decrease in ATP or total nucleic acid, and the cytotoxicity is completely rescued by simultaneous addition of nicotinic acid.
| ln Vitro |
GNE-617 hydrochloride's efficacy is assessed on 53 non-small cell lung cancer (NSCLC) cell lines with or without 10 μM nicotinic acid. NAMPT IC50 of 18.9 nM in A549 cells is inhibited by GNE-617.When measured by a drop in ATP or total nucleic acid, most cell lines show a steep dosage response to GNE-617; by adding nicotinic acid at the same time, the cytotoxicity is entirely mitigated. IC50 values for most studied cell lines are less than 100 nM, with about half having IC50 values less than 10 nM. Nicotinic acid is unable to save 18 cell lines, and these unsalvageable cell lines typically had lower IC50 values (P=0.008, Fisher exact test, IC50<10 nM vs. ≥10 nM)[1].
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| ln Vivo |
When compared to GMX-1778 (administered BID), GNE-617 hydrochloride (administered QD) and GNE-875 (administered BID) in rats are linked to more severe retinal toxicity at similar exposures and dosing durations. The purpose of the mouse efficacy studies utilizing GNE-617, GNE-618, and GMX-1778 is to evaluate efficacy and to evaluate retinal toxicity in mice in an opportunistic manner. GNE-617 and GMX-1778 both exhibit NAMPTi retinal toxicity; however, a direct comparison of their retinal toxicity is not possible due to their dissimilar study durations[2].
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| References |
[1]. Shames DS, et al. Loss of NAPRT1 Expression by Tumor-specific Promoter Methylation Provides a Novel Predictive Biomarker for NAMPT Inhibitors. Clin Cancer Res. 2013 Dec 15;19(24):6912-23.
[2]. Zabka TS, et al. Retinal toxicity, in vivo and in vitro, associated with inhibition of nicotinamide phosphoribosyltransferase. Toxicol Sci. 2015 Mar;144(1):163-72 |
| Molecular Formula |
C21H16CLF2N3O3S
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| Molecular Weight |
463.88
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| CAS # |
2070014-99-0
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| Related CAS # |
GNE-617;1362154-70-8
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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: ≥ 0.56 mg/mL (1.21 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 5.6 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: ≥ 0.56 mg/mL (1.21 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 5.6 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: ≥ 0.56 mg/mL (1.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1557 mL | 10.7786 mL | 21.5573 mL | |
| 5 mM | 0.4311 mL | 2.1557 mL | 4.3115 mL | |
| 10 mM | 0.2156 mL | 1.0779 mL | 2.1557 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.
Response of cancer cell lines to GNE-617 in the presence or absence of nicotinic acid.Clin Cancer Res.2013 Dec 15;19(24):6912-23. |
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NAPRT1 level determines nicotinic rescue status in cancer cell lines.Clin Cancer Res.2013 Dec 15;19(24):6912-23. |
NAPRT1 immunohistochemistry correlates with nicotinic acid rescue status.Clin Cancer Res.2013 Dec 15;19(24):6912-23. |
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