9-(2-Phosphonylmethoxyethyl)-N6-cyclopropyl-2,6-diaminopurine (cpr-PMEDAP) as a prodrug of 9-(2-Phosphonylmethoxyethyl)guanine (PMEG)

Biochemical Pharmacology

Volumn 58, Issue 4, 1999, Pages 709-714

  Compton, Mindy L ^a,b   Toole, John J ^a   Paborsky, Lisa R ^a  

^a GILEAD SCIENCES   (United States)

^b Axys Pharmaceuticals Inc   (United States)

Author keywords

Acyclic nucleotide analog; Antiproliferative activity; N6 cyclopropyl 2,6 diaminopurine; N6 deamination of a 2,6 diaminopurine nucleotide; Prodrug

Indexed keywords

DRUG METABOLITE; NUCLEOTIDE DERIVATIVE; PENTOSTATIN; PRODRUG; PURINE DERIVATIVE;

ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CARCINOMA CELL; CELL GROWTH; CELL PROLIFERATION; CONTROLLED STUDY; DEAMINATION; DRUG METABOLISM; HUMAN; HUMAN CELL; LIVER CYTOSOL; NONHUMAN; PANCREAS CARCINOMA; PHOSPHORYLATION; PRIORITY JOURNAL; RAT;

ADENINE; ANIMALS; ANTINEOPLASTIC AGENTS; ANTIVIRAL AGENTS; CELL DIVISION; DEAMINATION; DIDEOXYNUCLEOSIDES; GUANINE; HUMANS; ORGANOPHOSPHORUS COMPOUNDS; PRODRUGS; RATS; TUMOR CELLS, CULTURED;

EID: 0033567434     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0006-2952(99)00138-0     Document Type: Article

References (19)

1. Ho H.T., Woods K.L., Konrad S.A., De Boeck H., Hitchcock M.J.M. Cellular metabolism and enzymatic phosphorylation of 9-(2-phosphonylmethoxyethyl)guanine (PMEG), a potent antiviral agent. Block T., Jungkind D., Crowell R. Innovations in Antiviral Development and the Detection of Virus Infection. 1992;159-166 Plenum Press, New York.
2. Merta A., Votruba I., Jindrǐch J., Holý A., Cihlǎr T., Rosenberg I., Otmar M., Herve T.Y. Phosphorylation of 9-(2-phosphonomethoxyethyl)adenine and 9-(S)-(3-hydroxy-2-phosphonomethoxypropyl)adenine by AMP(dAMP) kinase from L1210 cells. Biochem Pharmacol. 44:1992;2067-2077.
3. Cihlǎr T., Votruba I., Horska K., Liboska R., Rosenberg I., Holý A. Metabolism of 1-(S)-(3-hydroxy-2-phosphonomethoxypropyl)cytosine (HPMPC) in human embryonic lung cells. Collect Czech Chem Commun. 57:1992;661-672.
4. Balzarini J., Hao Z., Herdewijn P., Johns D.G., De Clercq E. Intracellular metabolism and mechanism of anti-retrovirus action of 9-(2-phosphonylmethoxyethyl)adenine, a potent anti-human immunodeficiency virus compound. Proc Natl Acad Sci USA. 88:1991;1499-1503.
5. Merta A., Votruba I., Rosenberg I., Otmar M., Hřebabacký H., Bernaerts R., Holý A. Inhibition of herpes simplex virus DNA polymerase by diphosphates of acyclic phosphonylmethoxyalkyl nucleotide analogues. Antiviral Res. 13:1990;209-218.
6. Votruba I., Trávníěk M., Rosenberg I., Otmar M., Merta A., Hřebabecký H., Holý A. Inhibition of avian myeloblastosis virus reverse transcriptase by diphosphates of acyclic phosphonylmethyl nucleotide analogues. Antiviral Res. 13:1990;287-294.
7. De Clercq E. Broad spectrum anti-DNA virus and anti-retrovirus activity of phosphonylmethoxyalkylpurines and -pyrimidines. Biochem Pharmacol. 42:1991;963-972.
8. Naesens L., Balzarini J., Rosenberg I., Holý A., De Clercq E. 9-(2-Phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) A novel agent with anti-human immunodeficiency virus activity in vitro and potent anti-Moloney murine sarcoma virus activity in vivo . Eur J Clin Microbiol Infect Dis. 8:1989;1043-1047.
9. Paborsky L.R., Mao C.T., Toole J.J. Potent antiproliferative activity of a nucleotide analog, PMEG, against human solid tumor cell lines. Proc Am Assoc Cancer Res. 38:1997;100.
10. Rose W.C., Crosswell A.R., Bronson J.J., Martin J.C. In vivo antitumor activity of 9-[(2-phosphonylmethoxy)ethyl]guanine and related phosphonate nucleotide analogues. J Natl Cancer Inst. 82:1990;510-512.
11. Cihlǎr T., Chen M.S. Incorporation of selected nucleoside phosphonates and anti-human immunodeficiency virus nucleotide analogues into DNA by human DNA polymerases α, β and γ Antiviral Chem Chemother. 8:1997;187-195.
12. Pisarev V.M., Lee S.H., Connelly M.C., Fridland A. Intracellular metabolism and action of acyclic nucleoside phosphonates on DNA replication. Mol Pharmacol. 52:1998;63-68.
13. Kramata P., Downey K.M., Paborsky L.R. Incorporation and excision of 9-(2-phosphonylmethoxyethyl)guanine (PMEG) by DNA polymerases δ and ε in vitro. J Biol Chem. 273:1998;21966-21971.
14. Kramata P., Votruba I., Otová B., Holý A. Different inhibitory potencies of acyclic phosphonomethoxyalkyl nucleotide analogs toward DNA polymerases α, δ, and ε Mol Pharmacol. 49:1996;1005-1011.
15. Faletto M.B., Miller W.H., Garvey E.P., St. Clair MH, Daluge SM and Good SS, Unique intracellular activation of the potent anti-human immunodeficiency virus agent 1592U89. Antimicrob Agents Chemother. 41:1997;1099-1107.
16. Lowik C.W.G.M., Alblas M.J., van de Ruit M., Papapoulos S.E., van der Pluijm G. Quantification of adherent and nonadherent cells cultured in 96-well plates using the supravital stain neutral red. Anal Biochem. 213:1993;426-433.
17. Wohlhueter R.M., Plagemann P.G.V. Measurement of the transport versus metabolism in cultured cells. Methods Enzymol. 173:1989;714-733.
18. Huang P., Chubb S., Hertel L.W., Grindey G.B., Plunkett W. Action of 2′,2′-difluorodeoxycytidine on DNA synthesis. Cancer Res. 51:1991;6110-6117.
19. Huang P., Chubb S., Plunkett W. Termination of DNA synthesis by 9-β-arabinofuranosyl-2-fluoroadenine. A mechanism for cytotoxicity. J Biol Chem. 265:1990;4033-4040.