Reference

Clofarabine and nelarabine: two new purine nucleoside analogs

All Rights Reserved. Clofarabine and nelarabine: two new purine nucleoside analogs. Gandhi, Varsha; Plunkett, William (Departments of Experimental Therapeutics and Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA). Current Opinion in Oncology, 18(6), 584-590 (English) 2006 Lippincott Williams & Wilkins. CODEN: CUOOE8. ISSN: 1040-8746. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) Purpose of review: Both clofarabine and nelarabine recently received an accelerated approval by the US Food and Drug Administration for use in refractory or relapsed pediatric acute lymphoblastic leukemia and in refractory-relapsed T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. Both drugs have been studied for their metab. and mechanisms of action in preclin. investigations and for their efficacy in clin. trials.Several reagents with their cas registry numbers 121032-29-9 and 123318-82-1 are used here. This review will summarize these investigations and will suggest future plans with these nucleoside analogs. Recent findings: Clofarabine and nelarabine were designed based on preclin. and clin. findings with other nucleoside analogs or normal deoxynucleotides such as dGTP. Studies in cell lines have demonstrated that triphosphate is the active metabolite for both these purine nucleoside analogs. Pharmacokinetic and pharmacodynamic investigations during clin. trials have verified the importance of triphosphate levels in achieving clin. responses. Several phase I and II clin. explorations have suggested the utility of clofarabine in acute leukemias and nelarabine in T-cell diseases. Dose-limiting toxicities were nonhematol.: hepatotoxicity for clofarabine and neurotoxicity for nelarabine. Summary: Clofarabine is the first deoxyadenosine analog that shows promise in adult and pediatric acute leukemias without untoward toxicity. Nelarabine, as expected from its design, is a drug that may be directed to T-cell diseases. .

Novel purine nucleoside analogues for T-cell-lineage acute lymphoblastic leukemia and lymphoma

All Rights Reserved. Novel purine nucleoside analogues for T-cell-lineage acute lymphoblastic leukemia and lymphoma.In this study， 121032-29-9 and 209799-67-7 are also used. Ravandi, Farhad; Gandhi, Varsha (Departments of Leukaemia, Unit 428, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA). Expert Opinion on Investigational Drugs, 15(12), 1601-1613 (English) 2006 Informa Healthcare. CODEN: EOIDER. ISSN: 1354-3784. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review. Purine nucleoside phosphorylase (PNP) deficiency is a rare, inherited immunodeficiency disorder in which the specific mol. defect was identified. Clin., a lack of PNP manifests as profound T-cell deficiency with minor or variable changes in the humoral system. Biochem., 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 analogs as potential anti-T-cell-lineage agents over the past 30 years. Forodesine (an inhibitor of PNP) and nelarabine (a PNP-resistant dGuo analog) proved to be T-cell selective when tested in clinic. This review summarizes the preclin., clin. and pharmacokinetic investigations with these novel agents. .