GNE-617

SKU: orb1302942

Description

GNE-617 is a potent and specific inhibitor of NAMPT with an IC50 of 5 nM. It has demonstrated anti-tumor efficacy in cancer xenograft models, making it a valuable chemical probe for researching cancer metabolism in both in vitro and in vivo settings.

Research Area

Metabolism Research

Key Properties

• CAS Number: 1362154-70-8
• MW: 427.42
• Purity: 99.97% (May vary between batches)
• Formula: C₂₁H₁₅F₂N₃O₃S
• SMILES: Fc1cc(F)cc(c1)S(=O)(=O)c1ccc(CNC(=O)c2ccc3nccn3c2)cc1
• Target: NAMPT
• Solubility: DMSO:25 mg/mL (58.49 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (2.34 mM)

Bioactivity

• Target IC50:
  NAMPT:5 nM
• In Vivo:
  In rat studies, GNE-617 hydrochloride (QD) and GNE-875 (BID) demonstrated greater retinal toxicity at comparable exposures and durations of dosing than did GMX-1778 (BID). The efficacy studies in mice, which evaluated GNE-617, GNE-618, and GMX-1778, also opportunistically investigated retinal toxicity. NAMPTi-induced retinal toxicity was identified in cases involving GNE-617 and GMX-1778. However, varying study durations for GNE-617 and GMX-1778 preclude a direct comparison of their retinal toxicity profiles.
• In Vitro:
  In A549 cell, GNE-617 inhibits NAMPT (IC50=18.9 nM) .
• 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) .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Pre-B cell colony enhancing factor, Visfatin, NAMPT, Nicotinamide phosphoribosyl transferase, PBEF, Inhibitor, inhibit, GNE 617, GNE617, GNE-617

Compound Identifiers

PubChem CID

68277611