In vivo and in vitro pharmacologic activity of the purine nucleoside phosphorylase inhibitor BCX-34: The role of GTP and dGTP

Immunopharmacology

Volumn 35, Issue 1, 1996, Pages 53-63

  Bantia, Shanta ^a   Montgomery, John A ^a   Johnson, Harry G ^a   Walsh, Gerald M ^a  

^a BIOCRYST PHARMACEUTICALS INC   (United States)

Author keywords

BCX 34; deoxyguanosine triphosphate; guanosine triphosphate; peldesine; purine nucleoside phosphorylase; T cell proliferation

Indexed keywords

DEOXYCYTIDINE; DEOXYGUANOSINE; DEOXYGUANOSINE TRIPHOSPHATE; ENZYME INHIBITOR; ERYTHROCYTE ENZYME; GUANINE; GUANOSINE; GUANOSINE TRIPHOSPHATE; INOSINE; PELDESINE; PURINE NUCLEOSIDE PHOSPHORYLASE; PURINE NUCLEOSIDE PHOSPHORYLASE INHIBITOR; RADIOISOTOPE;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; ENZYME INHIBITION; ERYTHROCYTE; HUMAN; HUMAN CELL; INFLAMMATORY DISEASE; INTRAGASTRIC DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; LYMPHOCYTE PROLIFERATION; MALE; MOUSE; NONHUMAN; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; RAT; SKIN; T LYMPHOCYTE;

EID: 0030273182     PISSN: 01623109     EISSN: None     Source Type: Journal    
DOI: 10.1016/0162-3109(96)00123-3     Document Type: Article

References (27)

1. Allison, A.C. and Eugui, E.M., 1993. Immunosuppressive and other effects of mycophenolic acid and an ester prodrug, mycophenolate mofetil. Immunol. Rev. 136: 5-28.
2. Benear, J.B., Frederick, D., Townsend, L. and Epstein, R.B., 1986. Prolongation of skin graft survival in dogs treated with 8-aminoguanosine. Transplantation 41: 274-276.
3. Bennett, L.L., Jr., Allan, P.W., Noker, P.E., Rose, L.M., Niwas, S., Montgomery, J.A. and Erion, M.D., 1993. Purine nucleoside phosphorylase inhibitors: biochemical and pharmacological studies with 9-benzyl-9-deaza-guanine and related compounds. J. Pharmacol. Exp. Ther. 266: 707-714.
4. Carson, D.A., Kaye, J. and Wasson, D.B., 1980. Differences in deoxyadenosine metabolism in human and mouse lymphocytes. J. Immunol. 124: 8-12.
5. Chan, T., 1978. Deoxyguanosine toxicity on lymphoid cells as a cause for immunosuppression in purine nucleoside phosphorylase deficiency. Cell 14: 523-530.
6. Dong, M.K., Scott, M.E., Schrien D.J., Suto, M.J., Sircar, J.C., Black, A., Chang, T. and Gilbertsen, R.B., 1992. The biochemistry and pharmacology of PD 116124 (8-amino-2′-nordeoxyguanosine), an inhibitor of purine nucleoside phosphorylase (PNP). J Pharm Exp Ther 260: 319-326.
7. Eriksson, S., Thelander, L. and Kaerman, M., 1979. Allosteric regulation of calf thymus ribonucleoside diphosphate reductase. Biochemistry 18: 2948-2952.
8. Fox, I.H., Andres, C.M., Gelfand, E.W. and Biggar, D., 1977. Purine nucleoside phosphorylase deficiency: altered kinetic properties of a mutant enzyme. Science 197: 1084-1086.
9. Gilbertsen, R.B., Scott, M.E., Dong, M.K., Kossarek, L.M., Bennet, M.K., Schrier, D.J. and Sircar, J.C., 1987. Preliminary report on 8-amino-9-(2-thienylmethyl)guanine (PD 119,229), a novel and potent purine nucleoside phosphorylase inhibitor. Agents Actions 21: 272-274.
10. Gilbertsen, R.B., Josyula, U., Sircar, J.C., Dong, M.K., Wilburn, D.J. and Conroy, M.C., 1992. Comparative in vitro and in vivo activities of two 9-deazaguanine analog inhibitors of purine nucleoside phosphorylase. CI-972 and PD 141955. Biochem Pharmacol 44: 996-999.
11. Jenuth, J.P., Dilay, J.E., Fung, E., Mably, E.R., and Snyder, F.F., 1991. Absence of dGTP accumulation and compensatory loss of deoxyguanosine kinase in purine nucleoside phosphorylase deficient mice. In: eds. K.A. Harkness, et al., Purine and Pyrimidine Metabolism in Man VII, part B.; Plenum Press, New York, 273-332.
12. Kazmers, I.S., Mitchell, B.S., DaDonna, P.E., Wotring, I.I., Townsend, L.B. and Kelly, W.N., 1981. Inhibition of purine nucleoside phosphorylase by 8-aminoguanosine: selective toxicity for T-lymphocytes. Science 214: 1137-1139.
13. Krenitsky, T.A., Elion, G.B., Henderson, A.M. and Hitchings, G.H., 1968. Inhibition of human purine nucleoside phosphorylase. J. Biol. Chem. 243: 2876-2881.
14. Markert, M.L., 1991. Purine nucleoside phosphorylase deficiency. Immunodeficiency Rev. 3: 45-81.
15. Martin, A., Blattel, S., Fitzgibbon. J., Bartolucci, A. and Snyder, H., 1994. Treatment of cutaneous T-cell lymphoma with BCX-34 dermal cream. J. Invest. Dermatol. (abstract) 102: 614.
16. Montgomery, J.A., Niwas, S., Rose, J.D., Secrist, III, J.A., Babu, Y.S., Bugg, C.E., Erion, M.D., Guida, W.C. and Ealick, S.E., 1993a. Structure-based design of inhibitors of purine nucleoside phosphorylase: 9-(arylmethyl) derivatives of 9-deazaguanine. J. Med. Chem. 36: 55-69.
17. Montgomery, J.A., Snyder, H.W., Walsh, D.A. and Walsh, G.M., 1993b. BCX-34, purine nucleoside phosphorylase (PNP) inhibitor. Drugs Future 18: 887-890.
18. Osborne, W.R.A. and Barton, R.W., 1986. A rat model of purine nucleoside phosphorylase deficiency. Immunology 59: 63-67.
19. Osborne, W.R.A., 1986. Nucleoside Kinases in T and B lymphoblasts distinguished by autoradiography. Proc. Natl. Acad. Sci. 83: 4030-4034.
20. Simmonds, H.A., Watson, A.R., Webster, D.R., Sahota, A. and Perrett, D., 1982. GTP depletion and other erythrocyte abnormalities in inherited PNP deficiency. Biochem. Pharmacol. 31: 941-946.
21. Simmonds, H.A., Fairbanks, L.D., Morris, G.S., Morgan, G., Watson, A.R., Timms, P. and Singh, B., 1987. Central nervous system dysfunction and erythrocyte guanosine triphosphate depletion in purine nucleoside phosphorylase deficiency. Arch. Dis. Child. 62: 385-391.
22. Slichter, S.J., Deeg, H.J. and Osborne, W.R., 1990. Inhibition of the enzyme purine nucleoside phosphorylase (PNP) reduces refractoriness to transfused platelets in a dog model. British J. Haematol. 75: 591-597.
23. Snyder, F.F., Jemuth, J.P., Dilay, J.E., Fung, E., Lightfoot, T. and Mably, E.R., 1994. Secondary loss of deoxyguanosine kinase activity in purine nucleoside phosphorylase deficient mice. Biochim. Biophys. Acta 1227: 33-40.
24. Stoeckler, J.D., Ealick, S.E., Bugg, C.E. and Parks, R.E., Jr., 1986. Design of purine nucleoside phosphorylase inhibitors. Federation Proc. 45: 2773-2778.
25. Stoeckler, J.D. and Parks, R.E., Jr., 1986. Purine nucleoside phosphorylase. Measurement of activity and use of inhibitors. Meth. Pharmacol. 6: 147-162.
26. Walsh, G.M., Reddy, N.S., Bantia, S., Babu, Y.S. and Montgomery, J.A., 1994. Development of inhibitors of Purine Nucleoside Phosphorylase. Hematol. Rev. 8: 87-97.
27. Yen, C.Y., Chen, J.W. and Wang, H.H., 1990. A new immunosuppressant: T lymphocyte purine nucleoside phosphorylase inhibitor-8ABG on animal allograft studies. Chin. Pharm. J. 42: 249-256.