Nelarabine is a new member of the purine nucleoside antimetabolite class of
drugs. It was launched as an intravenous infusion for treating relapsed
or refractory T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic
lymphoma (T-LBL) after at least two prior chemotherapy regimens.
Nelarabine is a pro-drug of 9-b-D-arabinofuranosylguanine (ara-G), a deoxyguanosine
derivative with a high level of T-cell selective cytotoxicity. Although
Ara-G has been known since the 1960s, it has not been used in clinical studies
due to its poor solubility. Nelarabine is the O-methyl derivative of ara-G with
approximately 10 times greater aqueous solubility. It is demethylated in vivo by
adenosine deaminase to produce ara-G, which is subsequently converted to the
active 5’-triphosphate, ara-GTP. Accumulation of ara-GTP in leukemic blasts
allows for incorporation into DNA, leading to inhibition of DNA synthesis and
cell death.
