AGI-6780

AGI-6780 is a potent and selective inhibitor of IDH2 R140Q mutant with IC50 of 23 nM. (In Vitro) :AGI-6780 is tested in both human glioblastoma U87 and TF-1 cells expressing IDH2R140Q, as well as against IDH1R132H for 48 h incubation, with IC50 of 11±2.6 nM, 18±0.51 nM, and >1 mM, respectivly.Treatment of TF-1R140Q cells with AGI-6780, at concentrations that lower 2HG to near-normal physiologic levels, restore expression of both HBG and KLF1 genes and the color change associated with differentiation. AGI-6780 can reverse the IDH2R140Q-induced differentiation block in TF-1 cells. Pretreatment with AGI-6780 (0.2 μM and 1 μM) markedly decreased the intracellular concentration of (R) -2-hydroxyglutarate in the TF1R140Q cells and restored their ability to undergo EPO-induced differentiation.