AGI-6780

AGI-6780 that potently and selectively inhibits the tumor-associated mutant IDH2^R140Q with IC₅₀ of 23±1.7 nM. AGI-6780 is less potent against IDH2^WT with IC₅₀ of 190±8.1 nM. IC50 & Target: IC50: 23±1.7 nM (IDH2^R140Q), 190±8.1 nM (IDH2^WT)^[1] In Vitro: AGI-6780 is tested in both human glioblastoma U87 and TF-1 cells expressing IDH2^R140Q, as well as against IDH1^R132H for 48 h incubation, with IC50 of 11±2.6 nM, 18±0.51 nM, and >1 mM, respectivly.Treatment of TF-1^R140Q 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 IDH2^R140Q-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 TF1^R140Q cells and restored their ability to undergo EPO-induced differentiation^[1].