forodesine and Neoplasms

forodesine has been researched along with Neoplasms* in 2 studies

Reviews

2 review(s) available for forodesine and Neoplasms

ArticleYear
Forodesine: review of preclinical and clinical data.
    Future oncology (London, England), 2010, Volume: 6, Issue:8

    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.

    Topics: Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Neoplasms; Purine Nucleosides; Purine-Nucleoside Phosphorylase; Pyrimidinones; T-Lymphocytes

2010
Drug evaluation: forodesine - PNP inhibitor for the treatment of leukemia, lymphoma and solid tumor.
    IDrugs : the investigational drugs journal, 2006, Volume: 9, Issue:10

    Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine-salvage metabolic pathway. In humans, the loss of functional PNP results in significant T-cell-mediated immunodeficiency (and may also affect B-cell function). Forodesine is a potent PNP inhibitor that acts by elevating plasma 2'-deoxyguanosine (dGuo) and intracellular deoxyguanosine triphosphate, which in turn affects deoxynucleotide-triphosphate pools and induces cell death by apoptosis. BioCryst Pharmaceuticals Inc, under license from the Albert Einstein College of Medicine, is developing intravenous and oral formulations of forodesine for the potential treatment of various T-cell and B-cell lymphomas and leukemias, as well as for solid tumors; MundiPharma AG is also investigating the drug for leukemia. Forodesine effectively inhibits T-cell proliferation in vitro in the presence of dGuo. In early clinical trials, forodesine has demonstrated an acceptable safety profile and indications of biological activity. Few drug-related serious adverse events have been reported, and generally only mild-to-moderate nonhematological toxicity has been observed. Forodesine has the potential to lead the development of other novel therapies with broad-based activity for hematological malignancies; the drug may also be useful for the treatment of a wide variety of other T-cell-mediated disorders, as well as for the potential treatment for other B-cell lymphomas/leukemias.

    Topics: Animals; Enzyme Inhibitors; Humans; Leukemia; Lymphoma; Neoplasms; Purine Nucleosides; Purine-Nucleoside Phosphorylase; Pyrimidinones; Structure-Activity Relationship

2006