Biological Activity:

AG-221 (Enasidenib) is a potent and selective inhibitor of IDH2 R140Q mutant with IC50 ~16 nM. It can reduce intracellular and extracellular levels of 2-HG in TF-1/IDH2 (R140Q) mutant cells in a dose-dependent manner. It can reduce IDH2 (R140Q)-induced GM-CSF-independent growth, reduce histone hypermethylation associated with elevated levels of 2-HG. In vivo treatment with AG-221 in U87MG IDH2 (R140Q) tumor xenograft model lead to a reduction in tumor 2-HG concentration. A dose dependent decrease in leukemia and evidence of normal differentiation was seen in AG-221 treated NOD/SCID mice engrafted with AMM7577-P2 cells. Now the drug is in clinical trials for IDH2 mutant-positive AML.

How to Use:

In vitro: AG-221 was used at 1 µM in vitro and cellular assays.
In vivo: AG-221 was dosed orally to mice bearing IDH2 mutant tumors at 5-50 mg/Kg once per day.


Reference:

• 1. http://investor.agios.com/phoenix.zhtml?c=251862&p=irol-publications
• 2. Chong-Hui Gu, et al. Crystalline forms of therapeutically active compounds and use thereof. (2015) PCT WO 2015018060