Abstract
Purine nucleoside Phosphorylase (PNP) is a purine salvage enzyme that catalyzes the reversible phosphorylation of guanine and hypoxanthine-based nucleosides to their respective purine bases. Patients with homozygous deficiency in PNP have markedly impaired T cell function with normal to elevated B cell function. Because of the sparing of B cell function in PNP deficiency, inhibitors of PNP are purported to have the potential to be T cell selective immunosuppressive agents with application to a wide variety of clinical settings.1
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References
R.B. Gilbertsen and J.C. Sircar, Enzyme cascades: Purine metabolism and immunosuppression, in: “Comprehensive Medicinal Chemistry,” C. Hansch, P.G. Sammes, and J.B. Taylor, eds., Pergamon Press, New York (1990).
R.B. Gilbertsen, U. Josyula, J.C. Sircar, M.K. Dong, W. Wu, DJ. Wilburn, and M.C. Conroy, Comparative in vitro and in vivo activities of two 9-deazaguanine analog inhibitors of purine nucleoside Phosphorylase, CI-972 and PD 141955, Biochem. Pharm. 44: 996 (1992).
R.B. Gilbertsen and M.K. Dong, Effects of 8-aminoguanosine, an inhibitor of purine nucleoside Phosphorylase, on plasma nucleosides in Wistar rats, Annals New York Acad. Sci. 451: 313 (1985).
R.B. Gilbertsen, M.K. Dong, and L.M. Kossarek, Aspects of the purine nucleoside Phosphorylase (PNP) deficient state produced in normal rats following oral administration of 8-amino-9-(2-thienylmethyl)guanine (PD 119, 229), a novel inhibitor of purine nucleoside Phosphorylase, Agents and Actions 22: 379 (1987).
M.K. Dong, M.E. Scott, D.J Schrier, M.J. Suto, J.C. Sircar, A. Black, T. Chang and R.B. Gilbertsen, The biochemistry and pharmacology of PD 116124 (8-amino-2’-nordeoxyguanosine), an inhibitor of purine nucleoside Phosphorylase (PNP), J. Pharmacol. Exp. Ther. 260: 319 (1992).
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© 1995 Springer Science+Business Media New York
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Hallak, H., Hayes, A., Dong, M., Gilbertsen, R., Guttendorf, R. (1995). Pharmacokinetics/Pharmacodynamics of CI-1000, a Purine Nucleoside Phosphorylase (PNP) Inhibitor, in Rats and Monkeys. In: Sahota, A., Taylor, M.W. (eds) Purine and Pyrimidine Metabolism in Man VIII. Advances in Experimental Medicine and Biology, vol 370. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2584-4_36
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DOI: https://doi.org/10.1007/978-1-4615-2584-4_36
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