[CAS NO. 2070014-99-0] GNE-617hydrochloride
PRODUCTS SPECIFICATIONS [2070014-99-0]
DESCRIPTION [2070014-99-0]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 463.88 |
| Molecular Formula | C21H16ClF2N3O3S |
| SMILES | O=C(NCC1=CC=C(S(C2=CC(F)=CC(F)=C2)(=O)=O)C=C1)C3=CN4C(C=C3)=NC=C4.Cl |
3 Publications Citing Use of MCE
Summary
IC50 & Target
IC50: 5 nM (NAMPT) [1]
In Vitro
The activity ofGNE-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. The majority of the cell lines tested have IC 50 values below 100 nM, with approximately half with IC 50 values less than 10 nM. Eighteen cell lines are not rescued with nicotinic acid, and these non-rescuable cell lines tended to have lower IC 50 values (P=0.008, Fisher exact test, IC 50 <10 nM vs. ≥10 nM) [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
In rats, GNE-617 hydrochloride (administered QD) and GNE-875 (administered BID) are associated with more severe retinal toxicity at similar exposures and dosing duration compared with GMX-1778 (administered BID). The mouse efficacy studies using GNE-617, GNE-618, and GMX-1778 are designed to assess efficacy and opportunistically used to assess retinal toxicity in mice. NAMPTi retinal toxicity is observed with GNE-617 and GMX-1778; however, the different study durations between GNE-617 and GMX-1778 do not allow for direct comparison of retinal toxicity [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 5.56 mg/mL ( 11.99 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 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 |
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.