2. Cell Cycle/DNA Damage Metabolic Enzyme/Protease Apoptosis
  3. Eukaryotic Initiation Factor (eIF) Glutathione Peroxidase
  4. GCN2iB acetate

GCN2iB acetate is an ATP-competitive, selective GCN2 inhibitor with an IC50 of 2.4 nM. GCN2iB acetate inhibits the activation of the GCN2 pathway and upregulates GPX4. GCN2iB acetate enhances the anticancer effect of ASNase against acute lymphoblastic leukemia. GCN2iB acetate increases left ventricular ejection fraction, while reducing fasting blood glucose and myocardial fibrosis. GCN2iB acetate can be used in research related to acute lymphoblastic leukemia, acute myeloid leukemia and diabetic cardiomyopathy.

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CAS No. : 2183470-13-3

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GCN2iB acetate Related Antibodies

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60 Publications Citing Use of MCE GCN2iB acetate

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    GCN2iB acetate purchased from MedChemExpress. Usage Cited in: Cell Metab. 2023 Dec 5;35(12):2216-2230.e8.  [Abstract]

    FBXO22-WT and FBXO22-T127A-KI 293T-Endo-FLAG-FBXO22 cells were deprived of amino acids in the presence or absence of 1 μM GCN2iB and subjected to IP with an anti-FLAG antibody, followed by WB analysis of the indicated proteins.

    GCN2iB acetate purchased from MedChemExpress. Usage Cited in: Cell Metab. 2023 Dec 5;35(12):2216-2230.e8.  [Abstract]

    293T and HeLa cells deprived of amino acids for the indicated times were treated with or without 1 μM GCN2iB, followed by WB analysis of the indicated proteins.

    GCN2iB acetate purchased from MedChemExpress. Usage Cited in: Cell Metab. 2023 Dec 5;35(12):2216-2230.e8.  [Abstract]

    HeLa-Endo-Flag-FBXO22 cells were cultured in normal medium or amino-acidfree medium containing DMSO or 1 μM GCN2iB for 60 min, then subjected to Duolink. PLA assay with anti-Flag and anti-mTOR antibodies (top). PLA dots per cell (mean ±SEM) from n = 8 images were calculated (bottom).

    GCN2iB acetate purchased from MedChemExpress. Usage Cited in: Cell Metab. 2023 Dec 5;35(12):2216-2230.e8.  [Abstract]

    293T-Endo-HA-mTOR cells were treated with 100 ng/mL borrelidin (Bor) or 200 ng/mL halofuginone (HF) in the presence or absence of 1 μM GCN2iB for 4 h, followed by WB analysis of the indicated proteins.

    GCN2iB acetate purchased from MedChemExpress. Usage Cited in: Cell Metab. 2023 Dec 5;35(12):2216-2230.e8.  [Abstract]

    293T-Endo-Flag-FBXO22 cells were treated with 200 ng/mL halofuginone (HF) in the presence or absence of 1 μM GCN2iB for 4 h, and subjected to IP with an anti-Flag antibody, followed by WB analysis of the indicated proteins.

    GCN2iB acetate purchased from MedChemExpress. Usage Cited in: FASEB J. 2023 Mar;37(3):e22820.  [Abstract]

    GCN2iB (1 μM; 12 h) significantly inhibits Cholic acid (CA)-induced phosphorylation of GCN2 and eIF2α in HTR8/SVneo cells.

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    GPX1 GPX4

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    Description

    GCN2iB acetate is an ATP-competitive, selective GCN2 inhibitor with an IC50 of 2.4 nM. GCN2iB acetate inhibits the activation of the GCN2 pathway and upregulates GPX4. GCN2iB acetate enhances the anticancer effect of ASNase against acute lymphoblastic leukemia. GCN2iB acetate increases left ventricular ejection fraction, while reducing fasting blood glucose and myocardial fibrosis. GCN2iB acetate can be used in research related to acute lymphoblastic leukemia, acute myeloid leukemia and diabetic cardiomyopathy[1][2].

    IC50 & Target[1]

    GPX4

     

    GCN2

    2.4 nM (IC50)

    In Vitro

    GCN2iB (1 μmol/L) acetate potently inhibits recombinant GCN2 with an IC50 of 2.4 nmol/L, and exhibits high kinase selectivity, showing only extremely low off-target inhibitory activity in a screening panel containing 468 kinases[1].
    GCN2iB (10-9-10-5 M; 72 h) acetate enhances the antiproliferative effect of ASNase in GCN2-WT MEF cells, but shows no such effect in GCN2-KO MEF cells, confirming its inhibitory activity targeting GCN2[1].
    GCN2iB (1 μmol/L; 72 h) acetate sensitizes CCRF-CEM, MV-4-11 and SU.86.86 cells to the antiproliferative effect induced by ASNase[1].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    GCN2iB acetate Related Antibodies

    Cell Proliferation Assay[1]

    Cell Line: GCN2-WT MEF cells
    Concentration: 10-9-10-5 M
    Incubation Time: 72 h
    Result: Exhibited no antiproliferative effect when combined with ASNase in GCN2-KO MEF cells.
    Robustly reduced viability of cells when combined with ASNase in GCN2-WT MEF cells.
    In Vivo

    GCN2iB (10 mg/kg; twice daily; for 7 consecutive days) acetate acts synergistically with 1,000 U/kg ASNase to potently inhibit the growth of CCRF-CEM acute lymphoblastic leukemia (ALL) xenografts in mice, with a statistically significant interaction (P = 0.0007)[1].
    GCN2iB (10 mg/kg; twice daily; 3 days per week; for 28 consecutive days) acetate acts synergistically with 1,000 U/kg ASNase to improve the survival rate of mice with disseminated MOLT-3 acute lymphoblastic leukemia (ALL)[1].
    GCN2iB (3 mg/kg; i.p.; once every other day; for 6 consecutive weeks) acetate improves cardiac systolic function in diabetic mice induced by high-fat diet combined with Streptozotocin (HY-13753), increases left ventricular ejection fraction by 34.7%, and simultaneously reduces fasting blood glucose, myocardial lipid accumulation, oxidative stress and fibrosis[2].
    GCN2iB (3 mg/kg; intraperitoneal injection; once every 2 days; for 6 consecutive weeks) acetate improves cardiac systolic function in db/db mice, increases left ventricular ejection fraction by 14.5%, while reducing fasting blood glucose, decreasing myocardial lipid accumulation and alleviating oxidative stress[2].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Model: SCID[1]
    Dosage: 10 mg/kg; co-administered with 1,000 U/kg ASNase
    Administration: twice daily; daily; 7 days
    Result: Did not significantly affect tumor growth (P = 0.99).
    Elicited potent antitumor activity (P = 0.0002) with synergistic effects (main effect of ASNase, P = 0.0053; main effect of GCN2iB, P = 0.0006; interaction effect, P = 0.0007) when combined with ASNase.
    Achieved a tumor growth inhibition resulting in a treatment over control (T/C) value significantly lower than vehicle, ASNase alone, or GCN2iB alone when combined with ASNase.
    Animal Model: C57BL/6J (male; diabetic cardiomyopathy induced by 8 weeks of high-fat diet + intraperitoneal streptozotocin injection, fasting blood glucose ≥ 11.1 mmol/L)[2]
    Dosage: 3 mg/kg
    Administration: i.p.; every other day; 6 weeks
    Result: Decreased fasting blood glucose to 11.18 mmol/L.
    Decreased body weight to 28.94 g.
    Increased left ventricular ejection fraction to 70.41%.
    Increased heart weight to body weight ratio.
    Decreased myocardial fibrosis, myocyte cross-sectional area, and cardiac triglyceride levels.
    Decreased mRNA levels of hypertrophic/fibrotic genes (ANP, BNP, β-MHC, Calm3, Collagen-I, Collagen-III) and lipid metabolism-related genes (CD36, Fasn, Plin4, Plin2, Pparγ, SCD1, Srebp1c).
    Decreased myocardial 3'-NT, 4-HNE, and superoxide levels.
    Upregulated antioxidative genes (Gpx1/4/7, Gstp1/2, Mt1, Prdx2, Trx2) and proteins (GPX4, PRDX2, TRX2).
    Decreased protein expression of ANP, FAS, and CIDEA.
    Increased myocardial phosphocreatine and taurine levels.
    Upregulated oxidative phosphorylation, glycolysis/gluconeogenesis, proteasome, and amino acid biosynthesis pathway genes.
    Downregulated hypertrophic cardiomyopathy, dilated cardiomyopathy, and PPAR signaling pathway genes associated with disease progression.
    Animal Model: leptin receptor deficient (db/db) (male; spontaneous type 2 diabetes due to leptin receptor deletion)[2]
    Dosage: 3 mg/kg
    Administration: i.p.; every other day; 6 weeks
    Result: Decreased fasting blood glucose to 9.64 mmol/L.
    Decreased body weight to 44.67 g.
    Decreased heart weight to 145.7 mg.
    Increased left ventricular ejection fraction to 84.05%.
    Decreased cardiac triglyceride, 3'-NT, and 4-HNE levels.
    Decreased mRNA levels of hypertrophic/fibrotic genes (β-MHC, BNP, Calm3, Collagen-I, Collagen-III) and lipid metabolism-related genes (Fasn, Srebp1c).
    Increased mRNA levels of oxidative phosphorylation genes (Atcg1, Atp5d, Atp5j1, Ndufa8, Ndufs6).
    Decreased protein expression of ANP, FAS, CD36, and Cidea.
    Increased protein expression of GPX4, PRDX2, and TRX2.
    Molecular Weight

    511.89

    Formula

    C20H16ClF2N5O5S
    CAS No.
    SMILES

    O=S(C1=CC(Cl)=CN=C1OC)(NC2=CC=C(C(C#CC3=CN=C(N=C3)N)=C2F)F)=O.CC(O)=O
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage

    Please store the product under the recommended conditions in the Certificate of Analysis.
    Purity & Documentation
    References
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    GCN2iB acetate Related Classifications

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    Keywords:

    GCN2iB2183470-13-3Eukaryotic Initiation Factor (eIF)Glutathione PeroxidaseeIF2αERKacute myelogenous leukemiaATF4asparagine synthetasepancreatic cancergeneral control nonderepressible 2 (GCN2) kinasep38 MAPKJNKacute lymphoblastic leukemiaInhibitorinhibitorinhibit

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