A comparison of the transportability, and its role in cytotoxicity, of clofarabine, cladribine, and fludarabine by recombinant human nucleoside transporters 193 | P a g e produced in three model expression systems. Molecular pharmacology

2-Chloro-9-(2-deoxy-2-fluoro--D-arabinofuranosyl)adenine (Cl-F-ara-A, clofarabine), a purine nucleoside analog with struc-tural similarity to 2-chloro-2-deoxyadenosine (Cl-dAdo, cladribine) and 9--D-arabinofuranosyl-2-fluoroadenine (F-ara-A, fludarabine), has activity in adult and pediatric leuke-mias. Mediated transport of the purine nucleoside analogs is believed to occur through the action of two structurally unre-lated protein families, the equilibrative nucleoside transporters (ENTs) and the concentrative nucleoside transporters (CNTs). The current work assessed the transportability of Cl-F-ara-A, Cl-dAdo, and F-ara-A in cultured human leukemic CEM cells that were either nucleoside transport-defective or possessed individual human nucleoside transporter types and in Xenopus laevis oocytes and Saccharomyces cerevisiae yeast that pro