| Name | AGI-5198 |
| Description | AGI-5198 (IDH-C35) is a potent and selective inhibitor of IDH1 R132H and R132C mutants, with IC50 values of 0.07 μM and 0.16 μM, respectively. |
| Cell Research | AGI-5198 is dissolved in DMSO.TS603 cells are grown in medium containing either AGI-5198 (1.5 μM) 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 (1 μM).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. |
| Kinase Assay | 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. |
| In vitro | AGI-5198 showed some anti-tumor efficacy against TS603 glioma cell line and dose-dependently inhibited R-2HG production. Under the condition of almost complete inhibition of R-2HG, AGI-5198 induced demethylation of histone H3K9me3, and induced the expression of genes related to glial gene differentiation. In genome-wide DNA methylation, AGI-5198 inhibited the growth of mIDH1-impaired IDH1 mutant, but wild-type growth was hardly affected.AGI-5198 significantly inhibited mutant IDH1 (R132H-IDH1 and R132C-IDH1), but did not inhibit the growth of wild-type IDH1 (IC50>100 μM) or IDH1 (IC50>100 μM) or wild-type IDH1 (IC50>100 μM), but very weakly inhibited any of the IDH2 isoforms (R140Q, R172K, wild-type) (IC50>100 μM). |
| In vivo | AGI-5198 showed some anti-tumor efficacy against TS603 glioma cell line and dose-dependently inhibited R-2HG production. Under the condition of almost complete inhibition of R-2HG, AGI-5198 induced demethylation of histone H3K9me3, and induced the expression of genes related to glial gene differentiation. In genome-wide DNA methylation, AGI-5198 inhibited the growth of mIDH1-impaired IDH1 mutant, but wild-type growth was hardly affected.AGI-5198 significantly inhibited mutant IDH1 (R132H-IDH1 and R132C-IDH1), but did not inhibit the growth of wild-type IDH1 (IC50>100 μM) or IDH1 (IC50>100 μM) or wild-type IDH1 (IC50>100 μM), but very weakly inhibited any of the IDH2 isoforms (R140Q, R172K, wild-type) (IC50>100 μM). |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | DMSO : 23 mg/mL (49.7 mM)
Ethanol : 12 mg/mL (25.9 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| Keywords | Inhibitor | Isocitrate Dehydrogenase (IDH) | inhibit | AGI 5198 | AGI5198 | AGI-5198 |
| Inhibitors Related | Disulfiram | Methotrexate | ALDH1A3-IN-3 | Rotenone | Mycophenolate Mofetil | Ribavirin | 4-Diethylaminobenzaldehyde | Benzyl alcohol | Isomalt | Isoniazid | Sodium Oxamate | Ivosidenib |
| Related Compound Libraries | Highly Selective Inhibitor Library | Glycometabolism Compound Library | Bioactive Compound Library | Glutamine Metabolism Compound Library | Inhibitor Library | Metabolism Compound Library | Lipid Metabolism Compound Library | Bioactive Compounds Library Max | Fluorochemical Library | Anti-Metabolism Disease Compound Library |
United States
