GCN2iB

SKU: orb1309637

Description

GCN2iB

Research Area

Cell Biology

Key Properties

• CAS Number: 2183470-12-2
• MW: 451.83
• Purity: 99.08%
• Formula: C₁₈H₁₂ClF₂N₅O₃S
• SMILES: COc1ncc(Cl)cc1S(=O)(=O)Nc1ccc(F)c(C#Cc2cnc(N)nc2)c1F
• Target: PERK,Autophagy
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (2.21 mM);H2O:< 0.1 mg/mL (insoluble);DMSO:56.5 mg/mL (125.05 mM)

Bioactivity

• Target IC50:
  GCN2:2.4 nM
• In Vivo:
  METHODS: HFD plus STZ-induced diabetic C57BL/6J mice were treated with intraperitoneal injection of GCN2iB (3 mg/kg) every other day for 6 weeks. At the end of the experiment, the mice were subjected to echocardiography. RESULTS After GCN2iB treatment, the fasting blood glucose level (11.18 ± 1.44 vs. 17.42 ± 2.57 mmol/L) and body weight (28.94 ± 2.05 vs. 32.54 ± 1.49 g) of type 2 diabetic mice were significantly reduced; GCN2iB treatment had no effect on heart weight. Significant effects, but increased heart weight to body weight ratio; GCN2iB treatment significantly improved cardiac systolic function and increased left ventricular (LV) ejection fraction (EF).
• In Vitro:
  METHODS: HEK293 cells were treated with 4 nM to 4 μM Gcn2iB for 6 h in the presence or absence of Halofuginone (HF) treatment to explore the concentration-dependent effect of Gcn2iB on ISR activation. RESULTS HF treatment resulted in increased levels of p-Gcn2, p-eIF2α, and Atf4, each of which decreased with increasing concentrations of Gcn2iB; p-Gcn2 induction decreased at 62.5 nM Gcn2iB or higher, and Atf4 induction decreased at 250 nM Gcn2iB; cells treated with Gcn2iB in the absence of HF exhibited a biphasic response to the induction of p-Gcn2, p-eIF2α, and Atf4, with increases in all three ISR markers observed in the range of 10 to 100 nM Gcn2iB; above 250 nM Gcn2iB, p-Gcn2 levels decreased to below those determined with vehicle, and Atf4 levels were not significantly induced; although Gcn2iB could inhibit Gcn2 stimulation by HF treatment, lower concentrations of Gcn2iB activated Gcn2 and the ISR in the absence of external stress.

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

Autophagy, Inhibitor, GCN2, GCN2iB, GCN-2iB, Eukaryotic Initiation Factor (eIF), inhibit

Compound Identifiers

PubChem CID

134814489