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GNE-617 is a novel, potent and 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. NAMPT is a pleiotropic protein with intra- and extra-cellular functions as an enzyme, cytokine, growth factor, and hormone. NAMPT is of interest in 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 |
Tested against 53 non-small cell lung cancer (NSCLC) cell lines, the efficacy of GNE-617 hydrochloride was assessed with and without 10 μM Nicotinic Acid. With an IC50 of 18.9 nM in A549 cells, GNE-617 inhibits NAMPT. When GNE-617 was added concurrently with nicotinic acid, the majority of cell lines exhibited a steep dose response as measured by decreases in ATP or total nucleic acids. This prevented any cytotoxicity. IC50 values were found for most tested cell lines to be below 100 nM, and for about half of them to be below 10 nM [1].
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| ln Vivo |
When rats were given equal doses and dosage durations, GNE-617 (QD dosing) and GNE-875 (BID dosing) were linked to more severe retinal damage than GMX-1778 (BID dosing). The purpose of mouse efficacy studies including GNE-617, GNE-618, and GMX-1778 is to evaluate the products' effectiveness as well as any appropriate retinal toxicity. NAMPTi retinal toxicity was noted with both GNE-617 and GMX-1778; however, a direct comparison of their retinal toxicity was not possible due to their dissimilar research lengths [2].
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| References |
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| Molecular Formula |
C₂₁H₁₅F₂N₃O₃S
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| Molecular Weight |
427.42
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| Exact Mass |
427.08
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| Elemental Analysis |
C, 59.01; H, 3.54; F, 8.89; N, 9.83; O, 11.23; S, 7.50
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| CAS # |
1362154-70-8
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| Related CAS # |
GNE-617 hydrochloride;2070014-99-0
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| PubChem CID |
68277611
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| Appearance |
White to off-white solid powder
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| LogP |
4.847
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
699
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(NCC1=CC=C(S(C2=CC(F)=CC(F)=C2)(=O)=O)C=C1)C3=CN4C(C=C3)=NC=C4
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| InChi Key |
XRDVXQQZLHVEQZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H15F2N3O3S/c22-16-9-17(23)11-19(10-16)30(28,29)18-4-1-14(2-5-18)12-25-21(27)15-3-6-20-24-7-8-26(20)13-15/h1-11,13H,12H2,(H,25,27)
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| Chemical Name |
N-[[4-(3,5-difluorophenyl)sulfonylphenyl]methyl]imidazo[1,2-a]pyridine-6-carboxamide
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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: ≥ 1.67 mg/mL (3.91 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 16.7 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: ≥ 1.67 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3396 mL | 11.6981 mL | 23.3962 mL | |
| 5 mM | 0.4679 mL | 2.3396 mL | 4.6792 mL | |
| 10 mM | 0.2340 mL | 1.1698 mL | 2.3396 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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