| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
| Targets |
Nicotinamide phosphoribosyltransferase (NAMPT).
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| ln Vitro |
In the NSCLC cell line Calu-6[1], GNE-618 lowers NAD levels with an EC50 of 2.6 nM. Calu-6 cells' sub-2N cell populations' quantity and cellularity are shown by GNE-618 (10–30 nM; 72 hours). Measure ATP (EC50 of 13.6 ± 1.8 nM) or total protein content (EC50 of 25.8 ± 4.2 nM) are two alternative assay formats that GNE-618 uses to measure the reduction in Calu-6 cell proliferation. [1]
GNE-618 inhibits human NAMPT with an IC50 of 6.1 nM. It reduces NAD+ levels in PC3 prostate cancer cells with an EC50 of 1.2 nM and inhibits the proliferation of A2780 ovarian cancer cells with an IC50 of 4.3 nM. By blocking NAMPT activity, GNE-618 depletes NAD+ levels and induces tumor cell death. The compound demonstrates anti-tumor activity in preclinical models. It is a potent inhibitor of NAMPT with high cellular potency. |
| ln Vivo |
In the STO #81 patient-derived gastric model, GNE-618 (100 mg/kg; sidewall; twice daily for 5 days) effectively reduced tumor growth by 88% and had an impact on body weight concentration [1].
In vivo, GNE-618 depletes NAD levels and induces tumor cell death, demonstrating anti-tumor activity. The compound has been investigated in preclinical models of cancer, including prostate cancer and ovarian cancer. Specific dosing regimens and detailed efficacy data are available in the primary literature. GNE-618 is a valuable tool for studying the role of NAMPT in cancer and for validating NAMPT as a therapeutic target. |
| Enzyme Assay |
NAMPT inhibition is assessed using in vitro biochemical assays with recombinant NAMPT enzyme and substrates (nicotinamide and ATP). The production of nicotinamide mononucleotide (NMN) is measured. IC50 values are calculated from dose-response curves. Cellular activity is assessed by measuring NAD+ levels in cells treated with GNE-618.
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| Cell Assay |
Cellular activity is evaluated in cancer cell lines, including PC3 prostate cancer cells and A2780 ovarian cancer cells. Cells are treated with GNE-618 at various concentrations (typically 0.001-100 µM) for 24-72 hours. NAD+ levels are measured by enzymatic cycling assays or LC-MS. Cell proliferation is measured by MTT, MTS, or CellTiter-Glo assays. ATP levels are measured by luciferase-based assays. Apoptosis is measured by caspase-3/7 activation or Annexin V staining.
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| Animal Protocol |
In vivo efficacy is studied in mouse xenograft models of cancer, including prostate cancer and ovarian cancer. GNE-618 is administered via various routes (oral, intraperitoneal) at doses determined from pharmacokinetic and tolerability studies. Tumor growth is measured by caliper twice weekly, and tumor volume is calculated. NAD+ levels are measured in tumor tissue. Pharmacodynamic markers including NAD+ depletion and apoptosis are assessed in tumor tissue.
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| ADME/Pharmacokinetics |
GNE-618 has a molecular formula of C21H15F3N4O3S and a molecular weight of 460.43 g/mol. CAS Number: 1362151-42-5. Purity: typically ≥98% by HPLC. The compound is a NAMPT inhibitor. It is soluble in DMSO. Storage: store at -20°C for long-term stability, protected from light and moisture. Detailed pharmacokinetic parameters including half-life, oral bioavailability, and plasma protein binding are available from the primary literature.
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| Toxicity/Toxicokinetics |
Specific toxicological data for GNE-618 are not extensively published. As a NAMPT inhibitor that depletes NAD+ levels, it may cause metabolic stress and toxicity in normal cells, particularly in tissues with high NAD+ turnover. The compound should be handled with appropriate safety precautions. It is for research use only and not for human therapeutic applications without appropriate regulatory approval. Standard laboratory safety practices should be followed, including the use of personal protective equipment and adequate ventilation.
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| References | |
| Additional Infomation |
GNE-618 is a research tool compound for studying NAMPT biology, NAD+ metabolism, and cancer metabolism. It is not approved for clinical use. The compound is a potent inhibitor of NAMPT, the key enzyme in the NAD+ salvage pathway. By depleting NAD+ levels, GNE-618 induces tumor cell death and demonstrates anti-tumor activity in preclinical models. GNE-618 is a valuable tool for understanding the role of NAD+ metabolism in cancer and for validating NAMPT as a therapeutic target. It is used in research to investigate the metabolic vulnerabilities of cancer cells and to develop new strategies for cancer therapy.
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| Molecular Formula |
C21H15F3N4O3S
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|---|---|
| Molecular Weight |
460.4290
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| Exact Mass |
460.081
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| CAS # |
1362151-42-5
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| PubChem CID |
66613669
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
765
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1=C([H])C([H])=C([H])C(C(F)(F)F)=C1[H])(C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])N([H])C(C1=C([H])N=C2C(C([H])=NN2[H])=C1[H])=O)(=O)=O
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| InChi Key |
LKBHAGGICJWHQQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H15F3N4O3S/c22-21(23,24)16-2-1-3-18(9-16)32(30,31)17-6-4-13(5-7-17)10-26-20(29)15-8-14-12-27-28-19(14)25-11-15/h1-9,11-12H,10H2,(H,26,29)(H,25,27,28)
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| Chemical Name |
N-[[4-[[3-(Trifluoromethyl)phenyl]sulfonyl]phenyl]methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide
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| Synonyms |
GNE-618 GNE 618 GNE618
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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 |
| 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) |
DMSO : ~125 mg/mL (~271.49 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.52 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 20.8 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: ≥ 2.08 mg/mL (4.52 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 20.8 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: ≥ 2.08 mg/mL (4.52 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 | 2.1719 mL | 10.8594 mL | 21.7188 mL | |
| 5 mM | 0.4344 mL | 2.1719 mL | 4.3438 mL | |
| 10 mM | 0.2172 mL | 1.0859 mL | 2.1719 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.
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