Phase I trial of the PNP inhibitor BCX-34 in the treatment of cutaneous T- cell malignancies. T lymphocytes are unable to overcome the competitive inhibition of the critical enzyme purine nucleoside phosphorylase resulting in accumulation of intercellular nucleosides with subsequent cell death. B-cells, as well as other cells, are able to metabolize the accumulated nucleosides through a bypass salvage pathway, and are thus not impacted by PNP inhibition. This Phase I trial has demonstrated the ability of the drug taken orally to be absorbed, and has provided critical pharmacologic data for the half life of PNP inhibitor BCX-334 as well as the in vivo ability to inhibit PNP intracellularly. No dose limiting toxicity has been noted to date, and the phase I trial continues with dose escalation.
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