GNE-618 is a novel, potent, orally bioactive inhibitor of nicotinamide phosphoribosyl transferase (NAMPT, IC50 = 6 nM) with anti-tumor activity. GNE-618 depletes NAD levels and induces tumor cell death.
Physicochemical Properties
| Molecular Formula | C21H15F3N4O3S |
| Molecular Weight | 460.4290 |
| Exact Mass | 460.081 |
| CAS # | 1362151-42-5 |
| PubChem CID | 66613669 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 3.3 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 32 |
| Complexity | 765 |
| Defined Atom Stereocenter Count | 0 |
| 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 |
| InChi Key | LKBHAGGICJWHQQ-UHFFFAOYSA-N |
| 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) |
| Chemical Name | N-[[4-[[3-(Trifluoromethyl)phenyl]sulfonyl]phenyl]methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide |
| Synonyms | GNE-618 GNE 618 GNE618 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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] |
| 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]. |
| References |
[1]. Dependence of tumor cell lines and patient-derived tumors on the NAD salvage pathway rendersthem sensitive to NAMPT inhibition with GNE-618. Neoplasia. 2013 Oct;15(10):1151-60. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~125 mg/mL (~271.49 mM) |
| 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. 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. 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 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 | 2.1719 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 |