2015 ASCPT: Systems Pharmacology Modeling of Decitabine and SGI-110

Summary

Acute myeloid leukemia (AML) is a tumor associated with myeloid line of blood cells, characterized by the abnormal rapid proliferation of white blood cells in the bone marrow. The most common approach for AML treatment is the reduction of abnormal cell proliferation rate which can be achieved by targeting the key stages of the cell cycle.

Decitabine is a well characterized hypomethylating agent (HMA), which is incorporated into DNA during the S-phase of cell cycle, inhibits methylation of antitumor genes and induces G2/M arrest. However, it has a very short half-life (15-35 min) after IV infusion due to rapid degradation by cytidine deaminase. SGI-110, a 2nd generation HMA was designed to increase the in vivo xposure/potential efficacy of its active metabolite decitabine. The aim of this effort was to explore how changes in exposure window of decitabine affect DNA demethylation and tumor cell proliferation in AML patients.

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2015 ASCPT: Systems Pharmacology Modeling of Decitabine and SGI-110