| Description |
AG-221（Enasidenib） is a first-in-class, oral, potent, reversible, selective inhibitor of the IDH2 mutant enzyme with IC50 of 12 nM. |
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Targets
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| In vitro |
The compound has been demonstrated to reduce 2-HG levels by >90% and reverse histone and deoxyribonucleic acid (DNA) hypermethylation in vitro, and to induce differentiation in leukemia cell models[2].
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| In vivo |
AG-221 is able to potently reduce 2HG found in the bone marrow, plasma and urine of engrafted mice. Treatment also induced a dose dependent, statistically significant, survival benefit.
A proliferative burst of the human specific CD45+ blast cells is followed by cellular differentiation as measured by the expression of CD11b, CD14 and CD15 and cell morphology after AG-221 treatment[2].
AG-221 treatment also restores megakaryocyte-erythroid progenitor (MEP) differentiation that is suppressed by mutant IDH2 expression and reverses the effects of mutant IDH2 on DNA methylation in mutant stem/progenitor cells. Clinical trials combining IDH2 inhibitors with other targeted AML therapies are warranted in order to increase therapeutic efficacy[1].
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COA
HPLC