title: Forodesine: review of preclinical and clinical data.
abstract: Purine nucleoside phosphorylase (PNP) is an important catalytic enzyme in the purine salvage pathway; its deficiency is associated with T-cell lymphopenia and with humoral deficiency. This clinical observation led to the investigation of PNP inhibitors and their possible clinical application in the management of hematologic malignancies, notably those of T-cell lineage. Forodesine is the most potent of the PNP inhibitors. Its effect appears to be linked to increased 2 -deoxyguanosine levels in plasma, which in turn is converted to 2 -deoxyguanosine triphosphate in target cells and disrupts DNA synthesis. Several preclinical studies have shown forodesine's effect against lymphocytes in vitro and in vivo, and these findings have led to several Phase I/II studies in patients with lymphoid neoplasms. Early clinical trials show that forodesine has promise as a single agent for the treatment of relapsed/refractory hematologic malignancies, and combination therapies might be warranted to improve clinical results.
authors.affiliation: Department of Leukemia, Unit 428, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Aref
authors.initials: A
authors.lastname: Al-Kali
authors.forename: Varsha
authors.initials: V
authors.lastname: Gandhi
authors.forename: Mohamad
authors.initials: M
authors.lastname: Ayoubi
authors.forename: Michael
authors.initials: M
authors.lastname: Keating
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D011684:Purine Nucleosides / Q000627:therapeutic use*; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors*; D011744:Pyrimidinones / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D011684:Purine Nucleosides; D011744:Pyrimidinones; C113101:forodesine; D011683:Purine-Nucleoside Phosphorylase