AGI-5198

Territorial Availability: Available through Bertin Technologies only in France

• Synonyms
  • N-[2-(cyclohexylamino)-1-(2-methylphenyl)-2-oxoethyl]-N-(3-fluorophenyl)-2-methyl-1H-imidazole-1-acetamide
• Correlated keywords
  • IDH-C35 IDHC35 IDH C35 inhibitors inhibits inhibitions isocitrates dehydrogenases IDH1 IDH-1 IDH 1 one ?-ketoglutarate 2OG 2 OG two 2-OG gliomas antitumor anti tumors anti-tumors 2-hydroxyglutarate hydroxyglutarates HGs 2-HG R132H mutants histones demethylations gliogenesis AGI5198 AGI 5198 potent selectives R132C in vitro TS603 TS-603 xenografts H3K9me3 genes gliogenic differentiations cancers enzymes activity actives metabolisms NADs NADPs NAD-dependent NADP-dependent dependents tricarboxylic acids cycles catalyzes oxidatives decarboxylations alpha ketoglutarates alpha-ketoglutarate carbons dioxides IDH1 IDH2 mutated mutations maps arginines residues catalytic pockets gains of functions NADPH-dependent NADPHs conversion AGI-5198 wild-type wilds types cells lines growths treatments periods induces expressions
• Product Overview:
  Isocitrate dehydrogenases (IDHs) are nicotinamide adenine dinucleotide (NAD+) and NAD phosphate (NADP+)-dependent enzymes in the tricarboxylic acid cycle that catalyze oxidative decarboxylation of isocitrate producing a-ketoglutarate (2-OG) and carbon dioxide. IDH1 and IDH2 are mutated in >70% of lower grade gliomas.{22138} The most common mutations map to arginine residues in the catalytic pockets of IDH1 (R132) or IDH2 (R140 and R172) and impart new gain of function catalytic activity leading to the NADPH-dependent conversion of 2-OG to 2-hydroxyglutarate (2-HG).{22135,22156,20681} AGI-5198 is a potent, selective inhibitor of IDH1 R132H and R132C mutants in vitro with IC50 values of 0.07 and 0.16 µM, respectively, but not wild-type IDH1, wild-type IDH2, or IDH2 mutants (IC50s > 100 ?M).{23141} AGI-5198 has been shown to have anti-tumor efficacy in the TS603 glioma cell line and to lower tumor 2?HG production in HT1080 and U87MG cells with IC50 values of 0.48 and 0.07 µM, respectively.{23140} In R132H-IDH1 glioma xenografts, AGI-5198 (450 mg/kg/day) caused 50-60% growth inhibition over a treatment period of three weeks with no affect in the growth of IDH1 wild-type glioma xenografts.{23141} Under conditions of near complete 2-HG inhibition, AGI-5198 can induce demethylation of histone H3K9me3 and expression of genes associated with gliogenic differentiation.{23141}