1. Metabolic Enzyme/Protease
  2. Isocitrate Dehydrogenase (IDH)
  3. Ivosidenib

Ivosidenib (AG-120) is an orally active inhibitor of isocitrate dehydrogenase 1 mutant (mIDH1) enzyme, it exhibits profound d-2-hydroxyglutatrate (2-HG) lowering in vivo. Ivosidenib (AG-120) has the potential for AML therapy due to its acceptable safety profile and clinical activity.

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CAS No. : 1448347-49-6

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Based on 19 publication(s) in Google Scholar

Other Forms of Ivosidenib:

Top Publications Citing Use of Products

    Ivosidenib purchased from MedChemExpress. Usage Cited in: Cancer Drug Resist. 2025 Apr 24:8:20.  [Abstract]

    Dose-response curves of SKOV3, CAOV3, and OVCAR4 detected by MTT assay treated with cisplatin and 0 μM, 1 μM, 5 μM, 10 μM, 20 μM, and 50 μM Ivosidenib for 72 h.

    Ivosidenib purchased from MedChemExpress. Usage Cited in: Cancer Drug Resist. 2025 Apr 24:8:20.  [Abstract]

    Quantification of cell colony number in SKOV3, CAOV3, and OVCAR4 cells treated with Ivosidenib (10 μM), Cisplatin, or their combination.

    Ivosidenib purchased from MedChemExpress. Usage Cited in: J Med Chem. 2023 Apr 13;66(7):5279-5288.  [Abstract]

    Ivosidenib is the most potent IDH1 R132H inhibitor, exhibiting similar binding affinities to wild-type IDH1 and IDH1 R132H, with KD values of 416 nM and 488 nM, respectively.

    Ivosidenib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2022 Aug 15;13(1):4785.  [Abstract]

    Inhibition (%) of IDH1 variants (400 nM) by Ivosidenib (10 µM) as determined by the NADPH absorbance assay. Errors: standard errors of the mean (n = 3 independent replicates measured on the same 96-well plate).

    Ivosidenib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2022 Aug 15;13(1):4785.  [Abstract]

    Non-denaturing MS analysis measuring binding of Ivosidenib to IDH1 variants. At 20 µM IDH1 variants are predominantly dimeric with 2 NADP(H) molecules bound-dashed line. Green background corresponds to binding of one Ivosidenib molecule. Final concentrations of Ivosidenib: 5 µM (4:1), 20 µM (1:1), and 160 µM (1:8). Cone-voltage: 100 V.

    Ivosidenib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2022 Aug 15;13(1):4785.  [Abstract]

    LN18 cells were treated with the inhibitors Ivosidenib (24 h), GSK864, FT-2102, IDH224, and DS-1001B in DMSO (final concentration: 5 µM). 2-HG levels were determined by anion-exchange chromatography coupled to MS51 (errors: standard errors of the mean, n = 4 independent replicates).

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    Description

    Ivosidenib (AG-120) is an orally active inhibitor of isocitrate dehydrogenase 1 mutant (mIDH1) enzyme, it exhibits profound d-2-hydroxyglutatrate (2-HG) lowering in vivo. Ivosidenib (AG-120) has the potential for AML therapy due to its acceptable safety profile and clinical activity[1].

    IC50 & Target

    IDH1

     

    Cellular Effect
    Cell Line Type Value Description References
    HT-1080 IC50
    8 nM
    Compound: 99; AG-120
    Antiproliferative activity against human HT-1080 cells assessed as cell growth inhibition incubated for 48 hrs by sulforhodamine B assay
    Antiproliferative activity against human HT-1080 cells assessed as cell growth inhibition incubated for 48 hrs by sulforhodamine B assay
    [PMID: 37235998]
    HT-1080 IC50
    8 nM
    Compound: 99; AG-120
    Antiproliferative activity against human HT-1080 cells harboring IDH1 R132H mutant measured after 72 hrs by MTT assay
    Antiproliferative activity against human HT-1080 cells harboring IDH1 R132H mutant measured after 72 hrs by MTT assay
    [PMID: 37235998]
    U-87MG ATCC IC50
    0.56 μM
    Compound: 2; AG-120
    Synergistic antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant assessed as inhibition of cell growth incubated for 48 hrs in presence of FK866 by CCK8 assay
    Synergistic antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant assessed as inhibition of cell growth incubated for 48 hrs in presence of FK866 by CCK8 assay
    [PMID: 38651495]
    U-87MG ATCC IC50
    0.98 μM
    Compound: 2; AG-120
    Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant assessed as inhibition of cell growth incubated for 72 hrs by CCK8 assay
    Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant assessed as inhibition of cell growth incubated for 72 hrs by CCK8 assay
    [PMID: 38651495]
    U-87MG ATCC IC50
    1.02 μM
    Compound: 2; AG-120
    Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay
    Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay
    [PMID: 38651495]
    U-87MG ATCC IC50
    100.06 μM
    Compound: 2; AG-120
    Antiproliferative activity against human U-87 MG cells harboring wildtype IDH1 assessed as inhibition of cell growth incubated for 24 hrs by CCK8 assay
    Antiproliferative activity against human U-87 MG cells harboring wildtype IDH1 assessed as inhibition of cell growth incubated for 24 hrs by CCK8 assay
    [PMID: 38651495]
    U-87MG ATCC IC50
    19 nM
    Compound: 99; AG-120
    Antiproliferative activity against human U-87 MG cells assessed as reduction in cell growth by CCK-8 assay
    Antiproliferative activity against human U-87 MG cells assessed as reduction in cell growth by CCK-8 assay
    [PMID: 37235998]
    U-87MG ATCC IC50
    19 nM
    Compound: 99; AG-120
    Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant measured after 72 hrs by MTT assay
    Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant measured after 72 hrs by MTT assay
    [PMID: 37235998]
    U-87MG ATCC IC50
    2.51 μM
    Compound: 2; AG-120
    Synergistic antiproliferative activity against human U-87 MG cells harboring wildtype IDH1 assessed as inhibition of cell growth incubated for 48 hrs in presence of FK866 by CCK8 assay
    Synergistic antiproliferative activity against human U-87 MG cells harboring wildtype IDH1 assessed as inhibition of cell growth incubated for 48 hrs in presence of FK866 by CCK8 assay
    [PMID: 38651495]
    U-87MG ATCC IC50
    3.06 μM
    Compound: 2; AG-120
    Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant assessed as inhibition of cell growth incubated for 24 hrs by CCK8 assay
    Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant assessed as inhibition of cell growth incubated for 24 hrs by CCK8 assay
    [PMID: 38651495]
    U-87MG ATCC IC50
    67.22 μM
    Compound: 2; AG-120
    Antiproliferative activity against human U-87 MG cells harboring wildtype IDH1 assessed as inhibition of cell growth incubated for 72 hrs by CCK8 assay
    Antiproliferative activity against human U-87 MG cells harboring wildtype IDH1 assessed as inhibition of cell growth incubated for 72 hrs by CCK8 assay
    [PMID: 38651495]
    U-87MG ATCC IC50
    89.34 μM
    Compound: 2; AG-120
    Antiproliferative activity against human U-87 MG cells harboring wildtype IDH1 assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay
    Antiproliferative activity against human U-87 MG cells harboring wildtype IDH1 assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay
    [PMID: 38651495]
    In Vitro

    Ivosidenib (AG-120) (0-13 μM; 48 hours) inhibits several IDH1-R132 mutants with potency similar IC50 values: IDH1-R132H (IC50=12 nM); IDH1-R132C (IC50=13 nM); IDH1-R132G (IC50=8 nM); IDH1-R132L (IC50=13 nM); IDH1-R132S (IC50=12 nM), respectively[1].

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

    In Vivo

    AG-120 (gavage administration; 50 mg/kg and 150 mg/kg) declines tumor 2-HG concentration rapidly, with maximum inhibition (92.0% and 95.2% at the 50 mg/kg and 150 mg/kg doses, respectively) achieved at -12 h post dose[1].

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

    Animal Model: Female nude BALB/c mice inoculated with HT1080 cells[1]
    Dosage: 50 mg/kg and 150 mg/kg
    Administration: Gavage administration; 50 mg/kg and 150 mg/kg
    Result: Showed robust tumor 2-HG reduction in mouse.
    Essai clinique
    Masse moléculaire

    582.96

    Formule

    C28H22ClF3N6O3

    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    SMILES

    ClC1=C([C@H](N(C2=CC(F)=CN=C2)C([C@H]3N(C4=NC=CC(C#N)=C4)C(CC3)=O)=O)C(NC5CC(F)(F)C5)=O)C=CC=C1

    Livraison

    Room temperature in continental US; may vary elsewhere.

    Stockage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 1 year
    -20°C 6 months
    Solvant et solubilité
    In Vitro: 

    DMSO : 100 mg/mL (171.54 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 1.7154 mL 8.5769 mL 17.1538 mL
    5 mM 0.3431 mL 1.7154 mL 3.4308 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.

    • Calculateur de molarité

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

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

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

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    Volume (start)

    V1

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    C2

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    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    90% Corn Oil

      Solubility: ≥ 5 mg/mL (8.58 mM); Clear solution

      This protocol yields a clear solution of ≥ 5 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 (50.0 mg/mL) to 900 μL Corn oil, and mix evenly.

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

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    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
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    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.
    Pureté et documentation

    Purity: 99.89%

    Références

    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 1.7154 mL 8.5769 mL 17.1538 mL 42.8846 mL
    5 mM 0.3431 mL 1.7154 mL 3.4308 mL 8.5769 mL
    10 mM 0.1715 mL 0.8577 mL 1.7154 mL 4.2885 mL
    15 mM 0.1144 mL 0.5718 mL 1.1436 mL 2.8590 mL
    20 mM 0.0858 mL 0.4288 mL 0.8577 mL 2.1442 mL
    25 mM 0.0686 mL 0.3431 mL 0.6862 mL 1.7154 mL
    30 mM 0.0572 mL 0.2859 mL 0.5718 mL 1.4295 mL
    40 mM 0.0429 mL 0.2144 mL 0.4288 mL 1.0721 mL
    50 mM 0.0343 mL 0.1715 mL 0.3431 mL 0.8577 mL
    60 mM 0.0286 mL 0.1429 mL 0.2859 mL 0.7147 mL
    80 mM 0.0214 mL 0.1072 mL 0.2144 mL 0.5361 mL
    100 mM 0.0172 mL 0.0858 mL 0.1715 mL 0.4288 mL
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    Nom du produit:
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