Abstract
Purine nucleoside phosphorylase (PNP) deficiency is a rare, inherited immunodeficiency disorder in which the specific molecular defect was identified. Clinically, a lack of PNP manifests as profound T-cell deficiency with minor or variable changes in the humoral system. Biochemically, the absence of PNP results in an increase in plasma deoxyguanosine (dGuo) and a T-cell-specific increase in intracellular deoxyguanosine triphosphate (dGTP). This observation has been the impetus for the search for either inhibitors of the enzyme or PNP-resistant dGuo analogues as potential anti-T-cell-lineage agents over the past 30 years. Forodesine (an inhibitor of PNP) and nelarabine (a PNP-resistant dGuo analogue) proved to be T-cell selective when tested in clinic. This review summarises the prerlinical, clinical and pharmacokinetic investigations with these novel agents.
Original language | English (US) |
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Pages (from-to) | 1601-1613 |
Number of pages | 13 |
Journal | Expert Opinion on Investigational Drugs |
Volume | 15 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2006 |
Keywords
- Arabinosylguanine
- BCX-1777
- Forodesine
- Nelarabine
- Purine nucleoside phosphorylase
- T-cell lymphoblastic leukaemia/lymphoma
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)