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

AGI-5198 (Synonyms: IDH-C35)

Cat. No.: HY-18082 Purity: 99.99%
Handling Instructions

AGI-5198 is a novel R132H-IDH1 inhibitor, used for cancer treatment.

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

AGI-5198 Chemical Structure

AGI-5198 Chemical Structure

CAS No. : 1355326-35-0

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 106 In-stock
Estimated Time of Arrival: December 31
5 mg USD 96 In-stock
Estimated Time of Arrival: December 31
10 mg USD 144 In-stock
Estimated Time of Arrival: December 31
50 mg USD 276 In-stock
Estimated Time of Arrival: December 31
100 mg USD 420 In-stock
Estimated Time of Arrival: December 31
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    AGI-5198 purchased from MCE. Usage Cited in: J Neurooncol. 2018 Jun;138(2):241-250.

    LN18 IDH1 R132H cells are either treated with vehicle (DMSO) or 1 μM AG-5198 for the indicated number of days. Cells are harvested and Fn14, PAR-4 and GAPDH levels are evaluated by Western blot analysis.

    AGI-5198 purchased from MCE. Usage Cited in: Cancer Res. 2018 Sep 25. pii: canres.1772.2018.

    IDH1R132H-mediated epigenetic silencing of TSGs is inhibited by cyclin F.

    AGI-5198 purchased from MCE. Usage Cited in: FASEB J. 2018 Jun 7:fj201800547R.

    Representative photomicrographs of cells that are plated on glass coverslips in the presence or absence of 1μM AGI-5198, treated with 5 or 10μM Cisplatin for 1 h, and fixed after 30 min. γ-H2AX is stained immunocytochemically (red) to demonstrate DNA DSBs and with DAPI (blue) to demonstrate DNA nucleus content.

    AGI-5198 purchased from MCE. Usage Cited in: ACS Med Chem Lett. 2015 Jun 22;6(8):948-52.

    Combination treatment. (a) Comparison of AZD-8055 and ABT-263 treatment in all cell lines. Red indicates sensitivity, while blue indicates resistance. (b) Depiction of synergism where the values shown are excess over Bliss Independence, a prediction of inhibition without synergism. Increased synergism is evident by an increased number, shown in red, while negative numbers in blue represent an antagonistic effect.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    AGI-5198 is a novel R132H-IDH1 inhibitor, used for cancer treatment.

    In Vitro

    Measurements of R-2HG concentrations in pellets of TS603 glioma cells demonstrates dose-dependent inhibition of the mutant IDH1 enzyme by AGI-5198. AGI-5198 does not impair colony formation of two patient-derived glioma lines that express only the wild-type IDH1 allele (TS676 and TS516)[1]. Cancer cells heterozygous for the IDH1(R132H) mutation exhibits less IDH-mediated production of NADPH, such that after exposure to ionizing radiation (IR), there are higher levels of reactive oxygen species, DNA double-strand breaks, and cell death compared with IDH1 wild-type cells. These effects are reversed by the IDH1(R132H) inhibitor AGI-5198[2].

    In Vivo

    AGI-5198 (450 mg/kg, p.o.) causes 50 to 60% growth inhibition of the tumor growth from human glioma xenografts. Tumors from AGI-5198- treated mice show reduced staining with an antibody against the Ki-67 protein. AGI-5198 does not affect the growth of IDH1 wild-type glioma xenografts[1].

    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 34 mg/mL (73.50 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.1619 mL 10.8094 mL 21.6188 mL
    5 mM 0.4324 mL 2.1619 mL 4.3238 mL
    10 mM 0.2162 mL 1.0809 mL 2.1619 mL
    *Please refer to the solubility information to select the appropriate solvent.
    References
    Kinase Assay
    [1]

    Inhibitory potency against the IDH2 R140Q and IDH2 R172K enzymes is determined in an endpoint assay in which the amount of NADPH remaining at the end of the reaction is measured by the addition of a large excess of diaphorase and resazurin. IDH2 R140Q is diluted to 0.25 μg/mL in 40 μL 1X Assay Buffer (150 mM NaCl, 50 mM potassium phosphate pH 7.5, 10 mM MgCl2, 10% glycerol, 2 mM B-ME, 0.03% BSA) and incubated for 16 hours at 25°C in the presence of 1 μL of compound in DMSO. The reaction is started with the addition of 10 μL of Substrate Mix (20 μM NADPH, 8 μM alpha-ketoglutarate, in 1X Assay Buffer) and incubated for 1 hour at 25°C. Then, remaining NADPH is measured by the addition of 25 μL of Detection Mix (36 μg/mL diaphorase, 18 μM resazurin in 1X Assay buffer), incubated for 5 minutes at 25°C, and read as described above. IDH2 R172K is assayed as for IDH2 R140Q with the following modifications: 1.25 μg/mL of protein is used, the Substrate Mix contained 50 μM NADPH and 6.4 μM alpha-ketoglutarate, and the compound is incubated for 1 hour before starting the reaction.

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

    Cell Assay
    [1]

    TS603 cells are grown in medium containing either AGI-5198 (1.5μM) or DMSO vehicle control. One week prior to harvest cells are ransferred to differentiation medium (DMEM F12; 15 mM HEPES; 0.06% glucose; B27 without vitamin A; N2; Insulin/transferrin; 1% FBS) containing freshly added retinoic acid (1μM). ChIP of non-crosslinked cells is then carried out using established ChIP methods. 350 μg of lysate is immunoprecipitated-using anti-H3K9Me3, H3K27me3 or Rabbit Control IgG. After washing, ChIP DNA is eluted from protein G beads and analyzed by RT-PCR using SYBR green. Relative occupancy is calculated using the standard curve method and fold enrichment versus IgG. Enrichment in AGI- 5198-treated cells is normalized to vehicle control. Means and standard deviation are calculated from 4 technical replicates.

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

    Animal Administration
    [1]

    SCID mice are injected subcutaneously with 106 glioma cells, which are suspended in 100 μL of a 50:50 mixture of growth media and Matrigel. Once tumors have reached a measurable size, mice are randomized into the indicated treatment groups.

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

    References
    Molecular Weight

    462.56

    Formula

    C₂₇H₃₁FN₄O₂

    CAS No.

    1355326-35-0

    SMILES

    FC1=CC=CC(N(C(C2=CC=CC=C2C)C(NC3CCCCC3)=O)C(CN4C=CN=C4C)=O)=C1

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 99.99%

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    Product Name:
    AGI-5198
    Cat. No.:
    HY-18082
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    AGI-5198

    Cat. No.: HY-18082