| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
NAMPT (IC50 = 5 nM)
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| 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].
GNE-617 hydrochloride is a specific inhibitor of NAMPT with an IC50 of 5 nM. It is a highly potent, selective, and competitive small-molecule inhibitor of NAMPT, the rate-limiting enzyme in the NAD+ salvage pathway. The compound effectively disrupts NAMPT enzymatic activity, leading to decreased levels of NAD+ in cellular systems. In cellular assays, GNE-617 inhibits NAMPT-mediated NAD+ production and suppresses proliferation of cancer cell lines. |
| 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].
In vivo, GNE-617 demonstrates efficacy in xenograft models of cancer. Administration results in significant modulation of tumor growth in a dose-dependent manner. The compound shows good pharmacokinetic properties with adequate exposure to achieve therapeutic concentrations. Biomarker analyses confirm target engagement and pathway modulation in tumor tissues. |
| Enzyme Assay |
NAMPT activity is measured using biochemical assays with recombinant NAMPT enzyme and appropriate substrates. IC50 values are determined from dose-response curves. Selectivity profiling is conducted against a panel of enzymes to establish the selectivity profile.
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| Cell Assay |
Cellular potency is evaluated in cancer cell lines by measuring NAD+ levels and cell proliferation using MTT or CellTiter-Glo assays. The compound's activity is evaluated on a panel of 53 non-small cell lung cancer (NSCLC) cell lines in the presence or absence of 10 μM nicotinic acid. Apoptosis induction and other functional endpoints are measured to characterize the cellular activity of the compound.
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| Animal Protocol |
30 mg/kg; oral
Rat In vivo efficacy is evaluated in xenograft models of cancer. GNE-617 hydrochloride is administered via appropriate routes at various doses. Tumor growth inhibition is monitored, and pharmacodynamic biomarkers are assessed in tumor tissues. Pharmacokinetic sampling is performed to correlate exposure with efficacy. |
| ADME/Pharmacokinetics |
GNE-617 hydrochloride demonstrates favorable pharmacokinetic properties with adequate exposure for in vivo efficacy studies. The hydrochloride salt form may offer advantages in solubility and formulation. Detailed PK parameters are available from preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicology data for GNE-617 hydrochloride are derived from preclinical safety studies. The compound shows an acceptable safety profile at therapeutic doses. Comprehensive toxicology assessments including genotoxicity, cardiotoxicity (hERG), and repeated-dose toxicity studies have been conducted as part of the development program.
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| References |
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| Additional Infomation |
GNE-617 hydrochloride has been investigated in preclinical development as a NAMPT inhibitor for cancer therapy. The compound represents a promising therapeutic approach for targeting NAD+ metabolism in cancer. Development status and specific indications may vary, and the compound remains an important tool for studying NAMPT biology and NAD+ metabolism in cancer.
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| Molecular Formula |
C21H16CLF2N3O3S
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|---|---|---|
| Molecular Weight |
463.8848
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| Exact Mass |
463.056
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| CAS # |
2070014-99-0
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| Related CAS # |
GNE-617;1362154-70-8
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| PubChem CID |
78357806
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
699
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC=C1CNC(=O)C2=CN3C=CN=C3C=C2)S(=O)(=O)C4=CC(=CC(=C4)F)F.Cl
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| InChi Key |
ZTSTYFYGGLTNMN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H15F2N3O3S.ClH/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);1H
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| Chemical Name |
N-[[4-(3,5-difluorophenyl)sulfonylphenyl]methyl]imidazo[1,2-a]pyridine-6-carboxamide;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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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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