Purine nucleoside phosphorylase inhibition as a novel therapeutic approach for B-cell lymphoid malignancies.

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Furman RR, Hoelzer D

Purine nucleoside phosphorylase inhibition as a novel therapeutic approach for B-cell lymphoid malignancies.

Semin Oncol. 2007 Dec;34(6 Suppl 5):S29-34.

PubMed ID

18086344 [ View in PubMed

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Abstract

Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of ribonucleosides and 2'-deoxyribonucleosides to their respective bases. Endogenous PNP deficiency leads to specific T-cell immunodeficiency, a genetic disease that has prompted the development of PNP inhibitors as potential therapies for T-cell-mediated diseases. PNP inhibition leads to the elevation of 2'-deoxyguanosine levels and accumulation of intracellular deoxyguanosine 5'-triphosphate, inducing cellular apoptosis. Forodesine is a highly potent, orally active, rationally designed PNP inhibitor that has shown activity in preclinical studies with malignant cells and clinical utility against T-cell acute lymphoblastic leukemia and cutaneous T-cell lymphoma. Additional preliminary findings support its use for the management of some B-cell malignancies.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Forodesine	Purine nucleoside phosphorylase	Protein	Humans	Unknown	Not Available	Details