Purine nucleoside phosphorylase inhibitors in T-cell malignancies

Current Opinion in Drug Discovery and Development

Volumn 7, Issue 2, 2004, Pages 243-247

  Bantia, Shanta ^a   Kilpatrick, John Michael ^a  

^a BIOCRYST PHARMACEUTICALS INC   (United States)

Author keywords

Apoptosis; BCX 1777; Deoxyguanosine; dGTP; Purine nucleoside phosphorylase; T cell malignancies

Indexed keywords

DEOXYGUANOSINE; DEOXYGUANOSINE TRIPHOSPHATE; IMMUCILLIN H; PURINE NUCLEOSIDE PHOSPHORYLASE INHIBITOR; ANTINEOPLASTIC AGENT; ENZYME INHIBITOR; PURINE NUCLEOSIDE PHOSPHORYLASE;

CLINICAL TRIAL; DRUG DESIGN; DRUG INHIBITION; HUMAN; NONHUMAN; REVIEW; T CELL LEUKEMIA; ANIMAL; CELL PROLIFERATION; DRUG ANTAGONISM; DRUG EFFECT; ENZYMOLOGY; IMMUNOLOGY; T CELL LYMPHOMA; T LYMPHOCYTE;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL PROLIFERATION; ENZYME INHIBITORS; HUMANS; LEUKEMIA, T-CELL; LYMPHOMA, T-CELL; PURINE-NUCLEOSIDE PHOSPHORYLASE; T-LYMPHOCYTES;

EID: 16644402367     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (27)

1. Bugg CE, Carson WM, Montgomery JA: Drugs by design. Sci Am (1993) 269(6):92-98.
2. Morris PE, Omura GA: Inhibitors of the enzyme purine nucleoside phosphorylase as potential therapy for psoriasis. Curr Pharm Des (2000) 6(9):943-959.
3. Sircar JC, Gilbertsen RB: Purine nucleoside phosphorylase (PNP) inhibitors: Potentially selective immunosuppressive agents. Drugs Future (1988) 13:653-668.
4. Markert ML: Purine nucleoside phosphorylase deficiency. Immunodefic Rev (1991) 3(1):45-81. A comprehensive review of clinical and biochemical abnormalities in PNP-deficient patients.
5. Giblett ER, Ammann AJ, Wara DW, Sandman R, Diamond LK: Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity. Lancet (1975) 1(7914):1010-1013.
6. Kazmers IS, Mitchell BS, DaDonna PE, Wotring LL, Townsend LB, Kelley WN: Inhibition of purine nucleoside phosphorylase by 8-aminoguanosine: Selective toxicity for T-lymphocyles. Science (1981) 214(4525):1137-1139.
7. Carson DA, Kave J, Seegmiller JE: Lymphospecific toxicity in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency: Possible role of nucleoside kinase(s). Proc Natl Acad Sci USA (1977) 74(12):5677-5681.
8. Dong MK, Gilbertsen RB: PD 141955 and Cl-972: 9-Deazaguanine analog purine nucleoside phosphorylase inhibitors. II. Effects on nucleoside catabolism in human and rat blood in vitro. Agents Actions (1993) 39(Spec No):C99-C101.
9. Kicska GA, Long L, Horig H, Fairchild C, Tyler PC, Furneaux RH, Schramm VL, Kaufman HL: Immucillin H, a powerful transition-state analog inhibitor of purine nucleoside phosphorylase, selectively inhibits human T-lymphocytes. Proc Natl Acad Sci USA (2001) 98(8):4593-4598.
10. Bantia S, Miller PJ, Parker CD, Ananth SL, Horn LL, Babu YS, Sandhu JS: Comparison of in vivo efficacy of BCX-1777 and ciclosporin in xenogeneic graft-vs-host disease: The role of dGTP in antiproliferative action of BCX-1777. Int Immunopharmacol (2002) 2(7):913-923.
11. Bantia S, Ananth SL, Parker CD, Horn LL, Upshaw R: Mechanism of inhibition of T-acute lymphoblastic leukemia cells by PNP inhibitor BCX1777. Int Immunopharmacol (2003) 3(6):879-887.
12. Postmantur R, Wang KK, Nath R, Gilbertsen RB: A purine nucleoside phosphorylase (PNP) inhibitor induces apoptosis via caspase-3-like protease activity in MOLT-4 T cells. Immunopharmacology (1997) 37(2-3):231-244.
13. Oliver FJ, Collins MK, Lopez-Rivas A: dNTP pools imbalance as a signal to initiate apoptosis. Experientia (1996) 52(10-11):995-1000.
14. Hirota Y, Yoshioka A, Tanaka S, Watanabe K, Otani T, Minowada J, Matsuda A, Ueda T, Wataya Y: Imbalance of deoxyribonucleoside triphosphates, DNA double-strand breaks, and cell death caused by 2-chlorodeoxyadenosine in mouse FM3A cells. Cancer Res (1989)49(4):915-919.
15. Miles RW, Tyler PC, Furneaux RH, Bagdassarian CK, Schramm VL: One-third-the sites transition-state inhibitors for purine nucleoside phosphorylase. Biochemistry (1998) 37(24):8615-8621.
16. Bantia S, Miller PJ, Parker CD, Ananth SL, Horn LL, Kilpatrick JM, Morris PE, Hutchison TL, Montgomery JA, Sandhu JS: Purine nucleoside phosphorylase inhibitor BCX-1777 (Immucillin-H) - a novel potent and orally active immunosuppressive agent. Int Immunopharmacol (2001) 1(6):1199-1210. Demonstration of in vitro and in vivo inhibition of T-cells by BCX-1777.
17. Singhal RL, Yeh YA, Szekeres T, Weber G: Increased deoxycytidine kinase activity in cancer cells and inhibition by difluorodeoxycytidine. Oncol Res (1992) 4(11-12):517-522.
18. Kawasaki H, Carrera C, Carson DA: Quantitative immunoassay of human deoxycytidine kinase in malignant cells. Anal Biochem (1992) 207(1):193-196.
19. Eriksson S, Arner E, Spasokoukotskaja T, Wang L, Karlsson A, Brosjo O, Gunven P, Julusson G, Liliemark J: Properties and levels of deoxynucleoside kinases in normal and tumor cells: Implications for chemotherapy. Adv Enzyme Regul (1994) 34:13-25.
20. Snyder FF, Jenuth JP, Mably ER, Mangat RK: Point mutations at the purine nucleoside phosphorylase locus impair thymocyte differentiation in the mouse. Proc Natl Acad Sciences USA (1997) 94(6):2522-2527.
21. Sandhu JS, Boynton E, Gorczynski R, Hozumi N: The use of SCID mice in biotechnology and as a model for human disease. Crit Rev Biotechnol (1996) 16(1):95-118.
22. Bush WW: Overview of transplantation immunology and the pharmacotherapy of adult solid organ transplant recipients: Focus on immunosuppression. AACN Clin Issues (1999) 10(2):253-269.
23. Lemley DE, Katz P: Therapeutic strategies in autoimmune disease: Cyclosporin A as a model agent. In Vivo (1988) 2(1):115-118.
24. Zachariae H, Steen Olsen T: Efficacy of ciclosporin A (CyA) in psoriasis: An overview of dose/response, indications, contraindications and side effects. Clin Nephrol (1995) 43(3):154-158.
25. Viegas TX, Omura GA, Stoltz RR, Kisicki J: Pharmacokinetics and pharmacodynamics of Peldesine (BCX-34), a purine nucleoside phosphorylase inhibitor, following single and multiple oral doses in healthy volunteers. J Clin Pharmacol (2000) 40(4):410-420.
26. Thomas DA, Wierda W, Faderl S, O'Brien S, Kornblau S, Koller C, Bantia S, Kiltpatrick MJ, Bennett JC Kantarjian, Ghandi V: Preliminary activity of intravenous BCX-1777 in aggressive T-cell malignancies. Blood (2003) 102:Abs 4772. Clinical findings in T-cell malignancy patients with BCX-1777 exposure.
27. BioCryst Pharmaceutical Inc: BloCryst receives Orphan Drug designation for BCX-1777. Press Release (2004):February 05.