What is the mechanism of action of ensidipine in treating leukemia?

Ensidipine (enasidenib) is an oral small molecule isocitrate dehydrogenase inhibitor and antineoplastic agent, indicated for the treatment of isocitrate dehydrogenase detected by FDA-approved tests2 (IDH2)Adult patients with relapsed or refractory acute myeloid leukemia(AML)mutations.

What is the mechanism of action of ensidipine in treating leukemia?

Ensidipine is a small molecule inhibitor of isocitrate dehydrogenase 2 (IDH2) enzyme. In vitro, ensidipinetargets mutantIDH2variants at concentrations approximately 40fold lower than the wild-type enzyme. n>R140Q, R172S and R172K. In the IDH2mutatedAML mouse xenograft model,ensidipine suppresses the mutantIDH2enzyme causes a decrease in 2-hydroxyglutarate(2-HG) levels and induces myeloid differentiation in vitro and in vivo. In blood samples from IDH2mutated AML patients, ensidipine reduced 2-HG levels, reduced blast counts, and increased the percentage of mature myeloid cells.

The mean volume of distribution of ensidipine (Vd) is 55.8 liters (CV% 29). In vitro, the human plasma protein binding rate of ensidipine is 98.5%, and the binding rate of its metabolite AGI-16903 is 96.6%. The terminal half-life of ensidipine is 7.9 days, and the average systemic clearance (CL/F) is 0.70 liters / hours (CV% 62.5). Eighty-nine percent (89%) of ensidipine is eliminated in feces and 11% is eliminated in urine. Excretion of unchanged ensidipine accounted for 34% of the radiolabeled drug in feces and 0.4% in urine. If you want to get more high-quality information, you can contact YaDE. YaDE will do its best to learn more about high-quality overseas drugs for you.