AGI-5198

Catalog No.S7185 Batch:S718501

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Technical Data

Formula

C27H31FN4O2
Molecular Weight 462.56 CAS No. 1355326-35-0
Solubility (25°C)* In vitro DMSO 24 mg/mL (51.88 mM)
Ethanol 14 mg/mL (30.26 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description AGI-5198 (IDH-C35) is the first highly potent and selective inhibitor of IDH1 R132H/R132C mutants with IC50 of 0.07 μM/0.16 μM.
Targets
R132H-IDH1 [1]
(Cell-free assay)		 R132C-IDH1 [1]
70 nM 0.16 μM
In vitro AGI-5198, potently inhibits mutant IDH1 (R132H-IDH1 and R132C-IDH1), but not wildtype IDH1 (IC50 > 100 μM) or any of IDH2 isoforms (R140Q, R172K, wildtype) (IC50 > 100 μM). AGI-5198, has been shown to have anti-tumor efficacy in the TS603 glioma cell line and to block R-2HG production in a dose-dependent manner. Under conditions of near-complete R-2HG inhibition, AGI-5198 induced demethylation of histone H3K9me3 and expression of genes associated with gliogenic differentiation. Blockade of mIDH1 impaired the growth of IDH1-mutant—but not IDH1–wild-type—glioma cells without appreciable changes in genome-wide DNA methylation. [1]
In vivo In R132H-IDH1 glioma xenografts, AGI-5198 (450 mg/kg/day) causes 50-60% growth inhibition over a treatment period of three weeks with no affect in the growth of IDH1 wild-type glioma xenografts. Tumors from AGI-5198-treated mice shows reduced staining with an antibody against the Ki-67 protein. But cleaved caspase-3 shows no differences between tumors from vehicle and AGI-5198–treated mice. [1]

Protocol (from reference)

Kinase Assay:

[1]
  • IDH enzyme activity

    Compound is prepared as 10 mM stock in DMSO and diluted to 50X final concentration in DMSO, for a 50 μL reaction mixture. IDH enzyme activity converting alpha-ketogluta rate to 2-hydroxyglutarate is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH enzyme activity in the direction of isocitrate to alpha-ketoglutarate conversion is measured by direct coupling of the NADPH production to conversion of resazurin to resorufin by diaphorase. In both cases, resorufin is measured fluorometrically at Ex544 Em 590.
Cell Assay:

[1]
  • Cell lines

    TS603

  • Concentrations

    0, 23.4, 93.8, 375, 3000 nM

  • Incubation Time

    --

  • Method

    soft-agar colony formation
Animal Study:

[1]
  • Animal Models

    IDH1 mutant glioma xenografts

  • Dosages

    150 mg/kg, 450 mg/kg per day

  • Administration

    gavage

Customer Product Validation

Data from [Data independently produced by , , J BIOL CHEM, 2018, doi:10.1074/jbc.RA117.001385]

Selleck's AGI-5198 has been cited by 14 publications

A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [ EBioMedicine, 2024, 102:105090] PubMed: 38547578
High-Content and High-Throughput Clonogenic Survival Assay Using Fluorescence Barcoding [ Cancers -Basel), 2023, 15(19)4772] PubMed: 37835466
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
Loss of FBXW7 Correlates with Increased IDH1 Expression in Glioma and Enhances IDH1-Mutant Cancer Cell Sensitivity to Radiation [ Cancer Res, 2022, 82(3):497-509] PubMed: 34737211
Poly(ADP-ribose) glycohydrolase inhibition sequesters NAD+ to potentiate the metabolic lethality of alkylating chemotherapy in IDH mutant tumor cells [ Cancer Discov, 2020, CD-20-0226] PubMed: 32606138
Poly(ADP-ribose) Glycohydrolase Inhibition Sequesters NAD+ to Potentiate the Metabolic Lethality of Alkylating Chemotherapy in IDH-Mutant Tumor Cells [ Cancer Discov, 2020, 10(11):1672-1689] PubMed: 32606138
Triptolide Suppresses IDH1-mutated Malignancy via Nrf2-driven Glutathione Metabolism [ Proc Natl Acad Sci U S A, 2020, 5;117(18):9964-9972] PubMed: 32312817
IDH1-R132H mutation radiosensitizes U87MG glioma cells via epigenetic downregulation of TIGAR. [ Oncol Lett, 2020, 19(2):1322-1330] PubMed: 31966064
RNA-Binding Protein HuR Regulates Both Mutant and Wild-Type IDH1 in IDH1-Mutated Cancer [ Mol Cancer Res, 2019, 17(2):508-520] PubMed: 30266754
Heterozygous IDH1R132H/WT created by "single base editing" inhibits human astroglial cell growth by downregulating YAP [ Oncogene, 2018, 37(38):5160-5174] PubMed: 29849122

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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