Clofarabine

Clofarabine is a purine nucleoside antimetabolite marketed in the United States and Canada as Clolar.

It is FDA-approved for treating relapsed or refractory acute lymphoblastic leukaemia (ALL) in children after at least two other types of treatment have failed.

Clofarabine is a second-generation purine nucleoside analog designed to overcome biological limitations observed with ara-A and fludarabine.

A 2´(S)-fluorine in clofarabine significantly increased the stability of the glycosidic bond in acidic solution and toward phosphorolytic cleavage as compared to fludarabine.

Clofarabine-5´-triphosphate is the active-metabolite, and it inhibits ribonucleotide reductase, resulting in a decrease cellular dNTP concentrations, which promotes greater incorporation of clofarabine-5´-triphosphate during DNA synthesis.