GCN2-IN-6

SKU: orb1709630

Description

GCN2-IN-6 is a potent, orally bioavailable dual inhibitor of the eIF2α kinases GCN2 and PERK. It demonstrates low nanomolar activity in enzymatic assays and cellular systems, making it a valuable chemical probe for researching the integrated stress response in cancer and neurodegenerative disease models.

Research Area

Signal Transduction

Key Properties

• CAS Number: 2183470-09-7
• MW: 485.29
• Purity: 98.00% (May vary between batches)
• Formula: C₁₉H₁₂Cl₂F₂N₄O₃S
• SMILES: Nc1ncc(cn1)C#Cc1c(F)ccc(NS(=O)(=O)c2cc(Cl)cc(CO)c2Cl)c1F
• Target: PERK
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (10.3 mM);DMSO:250 mg/mL (515.16 mM)

Bioactivity

• Target IC50:
  GCN2:1.8 nM (IC50, in-house enzymatic)|GCN2:9.3 nM (IC50, cellular assays)|PERK:0.26 nM (IC50, in-house enzymatic)|PERK:230 nM (cellular assays)
• In Vivo:
  GCN2-IN-6 ( 0.3-3 mg/kg;oral administration;for 8 hours;mice) treatment at 3 mg/kg suppresses both self-phosphorylation of GCN2 and the downstream effector ATF4 to the basal level following pretreatment with asparaginase.
• In Vitro:
  The moderate antiproliferative effects achieved by combining asparaginase and GCN2-IN-6 treatment are observed in GCN2-wildtype (WT) mouse embryonic fibroblast (MEF) cells but not in GCN2-knockout (KO) MEF. GCN2-IN-6 demonstrates suppression on p-GCN2, p-eIF2α, and ATF4 activated by asparaginase. To examine the impact of GCN2 inhibition on cancer cell proliferation, acute lymphoblastic leukemia (ALL) CCRFCEM cells are treated with GCN2-IN-6 (Compound 6d) in the presence of asparagine depleting agent asparaginase. Treatment with GCN2-IN-6 greatly sensitizes CCRF-CEM cells to asparaginase.

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

inhibit, Eukaryotic Initiation Factor (eIF), Inhibitor, GCN2, cellular assays, GCN2, in-house enzymatic, GCN2, GCN2 IN 6, GCN2IN6, GCN-2-IN-6, GCN2-IN-6, PERK, PERK, cellular assays, PERK, in-house enzymatic

Compound Identifiers

PubChem CID

137347437