Powder: -20°C for 3 years
In solvent: -80°C for 2 years
GNE-617, a specific NAMPT inhibitor(IC50=5 nM), shows potency in xenograft models of cancer.
Description | GNE-617, a specific NAMPT inhibitor(IC50=5 nM), shows potency in xenograft models of cancer. |
Targets&IC50 | NAMPT:5 nM |
In vitro | In A549 cell, GNE-617 inhibits NAMPT (IC50=18.9 nM) . |
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; nevertheless, the different study durations between GNE-617 and GMX-1778 do not allow for direct comparison of retinal toxicity. |
Kinase Assay | For RNA interference (RNAi), A549 cells are plated at 1,500 cells per well in 96-well plates, allowed to adhere for 24 hours, and transfected with 25 nM siRNA oligonucleotide using Dharmafect 4. Transfected cells are treated with the indicated concentrations of GNE-617 (0.1, 1 , 10 , 100 , and 1000 nM) for 72 hours and viability is evaluated with CellTiter-Glo. Lysates for detection of NAPRT1 protein are collected 72 hours after transfection of 1 million A549 cells in 10 cm dishes. For NAPRT1 re-expression, RERF-LC-MS cells are transfected with pCMV6-AC.NAPRT1 and empty vector pCMV6-AC using Amaxa Nucleofector technology and selected with Geneticin |
Cell Research | GNE-617 is dissolved in DMSO and stored, and then diluted with appropriate media before use.Cells are grown in RPMI-1640 medium supplemented with 10% FBS and 2 mM glutamine and passaged not more than 20 times after thawing. To determine the IC50 values and nicotinic acid rescue status, cells are treated with nine point dose titrations of GNE-617 with or without 10 μM nicotinic acid. At 96 hours post-drug addition, the GNE-617-treated cells are evaluated using CyQUANT Direct Cell Proliferation Assay followed by CellTiter-Glo Luminescent Cell Viability Assay quantified with a Wallac EnVision 2104 Multilabel Reader. IC50 values are calculated using XLfit 5.1. To examine the protein level, cells are lysed in ice-cold radioimmunoprecipitation assay buffer, run on SDS-PAGE (4%-12% Bis-Tris), and evaluated by Western blotting using antibodies directed against NAPRT1 and β-actin |
Animal Research | Male na?ve Sprague Dawley rats are administered once daily via oral gavage with GNE-617( 30?mg/kg), formulated as a solution in the vehicle of 60% polyethylene glycol (PEG 400)/10% ethanol/30% 5% dextrose in water (D5W) . |
Synonyms | GNE617, GNE 617 |
Molecular Weight | 427.43 |
Formula | C21H15F2N3O3S |
CAS No. | 1362154-70-8 |
Powder: -20°C for 3 years
In solvent: -80°C for 2 years
DMSO: 42.85 mg/mL
( < 1 mg/ml refers to the product slightly soluble or insoluble )
You can also refer to dose conversion for different animals. More
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GNE-617 1362154-70-8 代谢 NAMPT Pre-B cell colony enhancing factor Inhibitor GNE 617 GNE617 PBEF Visfatin Nicotinamide phosphoribosyl transferase inhibit inhibitor