In vitro
AGI-6780 potently reduce (R)-2-hydroxyglutarate (2HG) levels in cell lines ectopically overexpressing IDH2/R140Q with EC50 of 20 nM, with excellent selectivity against other dehydrogenases. AGI-6780 reverses the IDH2/R140Q-induced differentiation block in TF-1 cells, and induces blast differentiation in primary human IDH2/R140Q AML patient samples.
Biological Activity
agi-6780 is a potent and selective inhibitor of tumor-associated idh2/r140q mutation with ic50 value of 23 nm [1].agi-6780 could significantly reduce intracellular concentration of 2hg in the human glioblastoma tf1/r140q cells, as well as reverse idh2/r140q-mediated differentiation block in tf1 cells in the presence of epo. agi-6780 could restore klf1 and hemoglobin g1/2 expressions in the epo-induced tf1/r140q cells [1].
References
[1] wang f1, travins j, delabarre b, penard-lacronique v, schalm s, hansen e, straley k, kernytsky a, liu w, gliser c, yang h, gross s, artin e, saada v,mylonas e, quivoron c, popovici-muller j, saunders jo, salituro fg, yan s, murray s, wei w, gao y, dang l, dorsch m, agresta s, schenkein dp, biller sa, su sm, de botton s, yen ke. targeted inhibition of mutant idh2 in leukemia cells induces cellular differentiation. science. 2013 may 3;340(6132):622-6.
