Nelarabine

Nelarabine is a purine nucleoside analog that is used as a cytotoxic agent in hematological malignancies. Nelarabine is converted into arabinosyl-guanine (ara-G) in the blood, and ara-G is selectively accumulated in T cells and malignant T-lymphoid cells, where it is phosphorylated to produce ara-GTP and incorporated into DNA. (In Vitro) :Nelarabine (506U78) (0-20 μM; 48 h) induces cytotoxic effects in T-ALL cell lines.Nelarabine (5 or 2 μM; 48 h) promotes apoptosis in sensitive T-ALL cell lines and modulates PI3K/AKT/mTOR and MEK signaling.Nelarabine (10 μM; 0-48 h) resistance does not depend on expression of ENT1/2 transporters and is partly due to upregulation of PI3K, MEK, and Bcl2 signaling. (In Vivo) :Nelarabine (506U78) (130 mg/kg/day; i.v.; 5 days) reduces leukemic burden and extends mouse survival in NSG mice xenografted with luciferase-expressing U937 cells.