Enasidenib (AG-221) counteracts the alterations induced by mutant IDH2 on DNA methylation in mutant stem/progenitor cells, fostering differentiation and inhibiting the self-renewal capabilities of IDH2-mutant leukemia cells. These effects are notably intensified when Flt3ITD is concurrently inhibited. Enasidenib therapy leads to leukemic cell differentiation, evidenced by an increased CD11b+ population and a decreased c-Kit+ population in the peripheral blood within 2 weeks[2].
体内研究
In an IDH2-mutant acute myeloid leukemia (AML) primary xenograft mouse model, treatment with enasidenib markedly enhances survival[1].
Acting as a mutant IDH2 inhibitor, enasidenib reconfigures the epigenetic landscape of IDH2-mutant cells, promoting changes in self-renewal and differentiation in an in vivo IDH2-mutant AML model. Treatment doses of 10 mg/kg or 100 mg/kg twice a day result in a significant reduction of 2-hydroxyglutarate (2-HG) levels, achieving a 96.7% decrease from baseline. Additionally, in mice engrafted with Mx1-Cre IDH2R140QFlt3ITD AML cells, treatment with enasidenib (100 mg/kg twice a day) significantly lowers 2-HG levels, aligning with the targeted inhibition of mutant IDH2, thus effectively blocking the production of 2-HG mediated by mutant IDH2[2].
体外研究
Enasidenib (AG-221) counteracts the alterations induced by mutant IDH2 on DNA methylation in mutant stem/progenitor cells, fostering differentiation and inhibiting the self-renewal capabilities of IDH2-mutant leukemia cells. These effects are notably intensified when Flt3ITD is concurrently inhibited. Enasidenib therapy leads to leukemic cell differentiation, evidenced by an increased CD11b+ population and a decreased c-Kit+ population in the peripheral blood within 2 weeks[2].
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