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
Glaxo Wellcome (US)
A chemotherapy drug used in the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL).
ChEBI: A purine nucleoside in which O-methylguanine is attached to arabinofuranose via a beta-N9-glycosidic bond. Inhibits DNA synthesis and causes cell death; a prodrug of 9-beta /stereo >-D-arabinofuranosylguanine (ara-G).
Arranon (SmithKline Beecham).
T-cell acute lymphoblastic leukaemia (T-ALL)
T-cell lymphoblastic lymphoma (T-LBL)
The drug was synthesized by enzymatic coupling of arabinosyluracil
87, prepared according to literature and 2-amino-
6-methoxy purine 88 using purine nucleoside phosphorylase
(PNP) and uridine phosphorylase (UP) in phosphate buffer
for 30 days to give the nelarabine (XIII) in 48% yield.
Potentially hazardous interactions with other drugs
Nelarabine is a pro-drug of the deoxyguanosine analogue
Extensive metabolism by O-demethylation by adenosine
deaminase to form ara-G, which undergoes hydrolysis to
form guanine. In addition, some nelarabine is hydrolysed
to form methylguanine, which is O-demethylated to form
guanine. Guanine is N-deaminated to form xanthine,
which is further oxidised to yield uric acid.
Nelarabine and ara-G are partially eliminated by the
 cohen mh, johnson jr, massie t, et al. approval summary: nelarabine for the treatment of t-cell lymphoblastic leukemia/lymphoma. clin cancer res. september 2006. 18:5329–35.
 yesid alvarado, mary alma welch, ronan swords, john bruzzi, ellen schlette, francis j. giles. nelarabine activity in acute biphenotypic leukemia. leukemia research. november 2007. 31(11): 1600-1603.