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

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

For research use only. We do not sell to patients.

CAS No. : 2183470-12-2

Size Price Stock Quantity
Free Sample (0.1 - 0.2 mg)   Apply Now  
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 In-stock
Solution
10 mM * 1 mL in DMSO In-stock
Solid
5 mg In-stock
10 mg In-stock
25 mg In-stock
50 mg In-stock
100 mg In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 60 publication(s) in Google Scholar

Other Forms of GCN2iB:

GCN2iB Related Antibodies

Top Publications Citing Use of Products

60 Publications Citing Use of MCE GCN2iB

IP
WB
Others

    GCN2iB 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 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 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 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 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 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.

    View All Glutathione Peroxidase Isoform Specific Products:

    View All Isoforms
    GPX1 GPX4

    • Biological Activity

    • Purity & Documentation

    • References

    • Customer Review

    Description

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

    IC50 & Target[1]

    GCN2

    2.4 nM (IC50)

    GPX4

     

    In Vitro

    GCN2iB (1 μmol/L) 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) 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) 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 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) 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) 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) 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) 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

    451.83

    Formula

    C18H12ClF2N5O3S
    CAS No.
    Appearance

    Solid

    Color

    Off-white to light yellow

    SMILES

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

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 1 year
    -20°C 6 months
    Solvent & Solubility
    In Vitro: 

    DMSO : 50 mg/mL (110.66 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.2132 mL 11.0661 mL 22.1322 mL
    5 mM 0.4426 mL 2.2132 mL 4.4264 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    Mass
    =
    Concentration
    ×
    Volume
    ×
    Molecular Weight *

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

    ×
    Volume (start)

    V1

    =
    Concentration (final)

    C2

    ×
    Volume (final)

    V2

    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 1.67 mg/mL (3.70 mM); Clear solution

      This protocol yields a clear solution of ≥ 1.67 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (16.7 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% Corn Oil

      Solubility: ≥ 1.67 mg/mL (3.70 mM); Clear solution

      This protocol yields a clear solution of ≥ 1.67 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (16.7 mg/mL) to 900 μL Corn oil, and mix evenly.

    For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  50% PEG300    50% Saline

      Solubility: 2.5 mg/mL (5.53 mM); Suspended solution; Need ultrasonic

    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.83%

    SDS (396 KB)

    COA (247 KB) HNMR (156 KB) LCMS (94 KB)

    Handling Instructions (2659 KB)
    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 2.2132 mL 11.0661 mL 22.1322 mL 55.3305 mL
    5 mM 0.4426 mL 2.2132 mL 4.4264 mL 11.0661 mL
    10 mM 0.2213 mL 1.1066 mL 2.2132 mL 5.5331 mL
    15 mM 0.1475 mL 0.7377 mL 1.4755 mL 3.6887 mL
    20 mM 0.1107 mL 0.5533 mL 1.1066 mL 2.7665 mL
    25 mM 0.0885 mL 0.4426 mL 0.8853 mL 2.2132 mL
    30 mM 0.0738 mL 0.3689 mL 0.7377 mL 1.8444 mL
    40 mM 0.0553 mL 0.2767 mL 0.5533 mL 1.3833 mL
    50 mM 0.0443 mL 0.2213 mL 0.4426 mL 1.1066 mL
    60 mM 0.0369 mL 0.1844 mL 0.3689 mL 0.9222 mL
    80 mM 0.0277 mL 0.1383 mL 0.2767 mL 0.6916 mL
    100 mM 0.0221 mL 0.1107 mL 0.2213 mL 0.5533 mL
    • No file chosen (Maximum size is: 1024 Kb)
    • If you have published this work, please enter the PubMed ID.
    • Your name will appear on the site.

    GCN2iB Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    GCN2iB2183470-12-2Eukaryotic Initiation Factor (eIF)Glutathione PeroxidaseeIF2αERKacute myelogenous leukemiaATF4asparagine synthetasepancreatic cancergeneral control nonderepressible 2 (GCN2) kinasep38 MAPKJNKacute lymphoblastic leukemiaInhibitorinhibitorinhibit

    Your Recently Viewed Products:

    Inquiry Online

    Your information is safe with us. * Required Fields.

    Product Name

    		  

    Requested Quantity *

    Applicant Name *

    		 

    Salutation

    Email Address *

    		 

    Phone Number *

    Department

    		 

    Organization Name *

    City

    State

    Country or Region *

    		      

    Remarks

    Bulk Inquiry

    Inquiry Information

    Product Name:
    GCN2iB
    Cat. No.:
    HY-112654
    Quantity:
    MCE Japan Authorized Agent:

    Customer Review

    Thank You for Your Feedback!

    Request for HNMR Report

    Please fill out this form to request the QC report. We will send it to your Email address shortly.

    Your information is safe with us. * Required Fields.

    Product Name

    		  

    Lot #

    Applicant Name *

    		 

    Email Address *

    Phone Number

    		 

    Department *

    Organization Name *

    		 

    Country or Region *

    Remarks

    SAFETY DATA SHEET (SDS)

    English - EN (396 KB) Français - FR (396 KB) Deutsch - DE (396 KB) Norwegian - NO (396 KB) Español - ES (396 KB) Swedish - SV (396 KB) Italian - IT (396 KB) Korean - KR (396 KB) Portuguese - PT (396 KB)

    Request for HNMR Report

    We have received your request and will respond to you as soon as possible.