AGI-5198 (IDH-C35) is a potent and selective isocitrate dehydrogenase 1 (IDH1) inhibitor specifically against R132H/C mutants (mIDH1) with IC50 at 100 nM range. AGI-5198 does not inhibit wild-type IDH1 or any of the examined IDH2 isoforms (IC50 > 100 µM). AGI-5198 inhibits R-2-hydroxyglutarate (R-2HG) production by mIDH1. AGI-5198 also induces demethylation of histone H3K9me3 and expression of genes associated with gliogenic differentiation.
In both in vitro and in vivo studies, AGI-5198 inhibited the growth of glioma cells carrying mutated but not wild type IDH1, yet with no appreciable changes in genome-wide DNA methylation. These data suggest that mIDH1 may promote glioma growth through mechanisms beyond its well-characterized epigenetic effects. AGI-5198 could serve as a very useful chemical tool to probe the mechanism and treatment of mIDH1-carrying tumors
|Solubility:||Up to 25 mM in DMSO|
|Synonyms:||AGI-5198, AGI5198, IDH-C35|
Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage condition: For longer shelf life, store solid powder or DMSO solution at -20oC desiccated.
|1.||Rohle D, et al. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science. 2013; 340(6132):626-30. Pubmed ID: 23558169|