GS-9191 is a novel topical prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl)guanine with antiproliferative activity and possible utility in the treatment of human papillomavirus lesions

Antimicrobial Agents and Chemotherapy

Volumn 53, Issue 7, 2009, Pages 2777-2784

  Wolfgang, Grushenka H I ^a   Shibata, Riri ^a   Wang, Jianying ^a   Ray, Adrian S ^a   Wu, Sylvia ^a   Doerrfler, Edward ^a   Reiser, Hans ^a   Lee, William A ^a   Birkus, Gabriel ^a   Christensen, Neil D ^b   Andrei, Graciela ^c   Snoeck, Robert ^c  

^a GILEAD SCIENCES   (United States)

^b PENN STATE CANCER INSTITUTE   (United States)

^c REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

9 (2 PHOSPHONYLMETHOXYETHYL) 6 N CYCLOPROPYL 2,6 DIAMINOPURINE; 9 (2 PHOSPHONYLMETHOXYETHYL)GUANINE; 9 (2 PHOSPHONYLMETHOXYETHYL)GUANINE DIPHOSPHATE; CIDOFOVIR; DNA DIRECTED DNA POLYMERASE ALPHA; DNA DIRECTED DNA POLYMERASE BETA; DNA DIRECTED DNA POLYMERASE GAMMA; GS 9191; MITOCHONDRIAL DNA; NUCLEOTIDE DERIVATIVE; PLACEBO; PRODRUG; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CELL CYCLE S PHASE; CELL GROWTH; CONCENTRATION RESPONSE; CONTROLLED STUDY; DNA SYNTHESIS INHIBITION; DOSE RESPONSE; DRUG METABOLISM; DRUG POTENCY; ENZYME INHIBITION; FEMALE; FOLLOW UP; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MALE; NONHUMAN; OINTMENT; PAPILLOMA; PRIORITY JOURNAL; RABBIT; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT RESPONSE; TUMOR VOLUME; UTERINE CERVIX CARCINOMA; VIRUS INFECTION; VIRUS INHIBITION; WART VIRUS;

ANIMALS; ANTINEOPLASTIC AGENTS; ANTIVIRAL AGENTS; CELL CYCLE; CELL LINE; CELL LINE, TUMOR; CELL PROLIFERATION; CELLS, CULTURED; DNA-DIRECTED DNA POLYMERASE; FEMALE; GUANINE; HUMANS; MALE; PHENYLALANINE; PRODRUGS; RABBITS; UTERINE CERVICAL NEOPLASMS;

EID: 67650003697     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00103-09     Document Type: Article

References (28)

1. Andrei, G., R. Snoeck, J. Piette, P. Delvenne, and E. De Clercq. 1998. Antiproliferative effects of acyclic nucleoside phosphonates on human papillomavirus (HPV)-harboring cell lines compared with HPV-negative cell lines. Oncol. Res. 10:523-531.
2. Birkus, G., I. Vortruba, M. Otmar, and A. Holy. 2001. Interactions of 1-[(S)-3-hydroxy-2-(phosphonomethoxy)-propyl]cytosine (cidofovir) diphosphate with DNA polymerases α, δ, and ε. Collect. Czech. Chem. Commun. 66:1698-1706.
3. Birkus, G., R. Wang, X. Liu, N. Kutty, H. MacArthur, T. Cihlar, C. Gibbs, S. Swaminathan, W. Lee, and M. McDermott. 2007. Cathepsin A is the major hydrolase catalyzing the intracellular hydrolysis of the antiretroviral nucleotide phosphonoamidate prodrugs GS-7340 and GS-9131. Antimicrob. Agents Chemother. 51:543-550.
4. Brandsma J. L. 2005. The cottontail rabbit papillomavirus model of high-risk HPV-induced disease, p. 217-235. In C. Davy and J. Doorbar (ed.), Methods in molecular medicine, vol. 19. Humana Press, Inc. Totowa, NJ.
5. Centers for Disease Control and Prevention. 2006. Sexually transmitted diseases guidelines, 2006. MMWR Recommend. Rep. 55(RR11):1- 94.
6. Christensen, N. D. 2005. Cottontail rabbit papillomavirus (CRPV) model system to test antiviral and immunotherapeutic strategies. Antivir. Chem. Chemother. 16:355-362.
7. Christensen, N. D., M. D. Pickel, L. R. Budgeon, and J. W. Kreider. 2000. In vivo anti-papillomavirus activity of nucleoside analogues including cidofovir on CRPV-induced rabbit papillomas. Antivir. Res. 48:131-142.
8. Cihlar, T., and M. S. Chen. 1997. Incorporation of selected nucleoside phosphonates and anti-human immunodeficiency virus nucleotide analogues into DNA by human DNA polymerases α, β, and γ. Antivir. Chem. Chemother. 8:187-195.
9. 6-cyclopropyl-2-6-diaminopurine (cpr-PMEDAP) as a prodrug of 9-(2-phosphonylmethoxyethyl) guanine (PMEG). Biochem. Pharmacol. 58:709-714.
10. Duan, J., W. Paris, J. De Marte, D. Roopchand, T. L. Fleet, and M. G. Cordingley. 2000. Topical effects of cidofovir on cutaneous rabbit warts: treatment regimen and inoculum dependence. Antivir. Res. 46:135-144.
11. Finzer, P., A. Aguilar-Lemarroy, and F. Rosl. 2002. The role of human papillomavirus oncoproteins E6 and E7 in apoptosis. Cancer Lett. 188:15-24.
12. Fox, P. A., and M. Tung. 2005. Human papillomaviruses - burden of illness and treatment cost considerations. Am. J. Clin. Dermatol. 6:365-381.
13. 6-cyclopropyl-PMEDAP: a novel derivative of 9-(2- phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) with distinct metabolic, antiproliferative, and differentiation-inducing properties. Biochem. Pharmacol. 58:311-323.
14. Holy, A., I. Votruba, A. Merta, J. Cerny, J. Vesely, J. Vlach, K. Sediva, I. Rosenberg, M. Otmar, H. Hrebabecky, M. Trávníć ek, V. Vonka, R. Snoeck, and E. De Clercq. 1990. Acyclic nucleotide analogues: synthesis, antiviral activity and inhibitory effects on some cellular and virus-encoded enzymes in vitro. Antivir. Res. 13:295-311.
15. Kramata, P., I. Votruba, B. Otova, and A. Holy. 1996. Different inhibitory potencies of acyclic phosphonomethoxyalkyl nucleotide analogs toward DNA polymerases α, δ, and ε. Mol. Pharmacol. 49:1005-1011.
16. Kramata, P., K. M. Downey, and L. R. Paborsky. 1998. Incorporation and excision of 9-(2-phosphonylmethoxyethyl)guanine (PMEG) by DNA polymerase delta and epsilon in vitro. J. Biol. Chem. 273:21966-21971.
17. Kramata, P., and K. M. Downey. 1999. 9-(2-phosphonylmethoxyethyl) derivatives of purine nucleotide analogs: a comparison of their metabolism and interaction with cellular DNA synthesis. Mol. Pharmacol. 56:1262-1270.
18. Kreider, J. W., K. Balogh, R. O. Olson, and J. C. Martin. 1990. Treatment of latent rabbit and human papillomavirus infections with 9-(2-phosphonylmethoxy)ethylguanine (PMEG). Antivir. Res. 14:51-58.
19. Kreider, J. W., N. D. Christensen, C. B. Christian, and M. D. Pickel. 1992. Preclinical system for evaluating topical podofilox treatment of papillomas: dose-response and duration of growth prior to treatment. J. Investig. Dermatol. 99:813-818.
20. Longworth, M. S., and L. Laimins. 2004. Pathogenesis of human papillomaviruses in differentiating epithelia. Microbiol. Mol. Biol. Rev. 68:362-372.
21. Pisarev, V. M., S.-H. Lee, M. C. Connelly, and A. Fridland. 1997. Intracellular metabolism and action of acyclic nucleoside phosphonates on DNA replication. Mol. Pharmacol. 52:63-68.
22. Reiser, H., J. Wang, L. Chong, W. J. Watkins, A. S. Ray, R. Shibata, G. Birkus, T. Cihlar, S. Li B. Wu, X. Liu, I. N. Henne, G. H. I. Wolfgang, M. Desai, G. R. Rhodes, A. Fridland, W. A. Lee, W. Plunkett, D. Vail, D. H. Thamm, R. Jerai, and D. B. Tumas. 2008. GS-9219 - a novel prodrug of the acyclic nucleotide PMEG with potent anti-neoplastic activity in dogs with spontaneous non-Hodgkin's lymphoma. Clin. Cancer Res. 14:2824-2832.
23. Rose, W. C., A. R. Crosswell, J. J. Bronson, and J. C. Martin. 1990. In vivo tumor activity of 9-[(2-phosphonylmethoxy)ethyl]-guanine (PMEG) and related phosphonate nucleotide analogs. J. Natl. Cancer Inst. 82:510-512.
24. Sampath, J., M. Adachi, S. Hatse, L. Naesens, J. Balzarini, R. Flatley, L. Matherly, and J. Schuetz. 2002. Role of MRP4 and MRP5 in biology and chemotherapy. AAPS PharmSci. 4:E14.
25. Snoeck, R., M. Bossens, D. Parent, B. Delaere, H. Degreef, M. Van Ranst, J. C. Noël, M. S. Wulfsohn, J. F. Rooney, H. S. Jaffe, and E. De Clercq. 2001. Phase II double-blind, placebo-controlled study of the safety and efficacy of cidofovir topical gel for the treatment of patients with human papillomavirus infection. Clin. Infect. Dis. 33:597-602.
26. Thomson PDR. 2007. Physicians' desk reference, 61st ed. Thomson PDR, Montvale, NJ.
27. Von Krogh, G., C. J. N. Lacey, G. Gross, R. Barrasso, and A. Schneider. 2001. European guidelines for the management of anogenital warts. Int. J. of STD AIDS 12(Suppl. 3):40-47.
28. Yan, J., S. L. Chen, H. N. Wang, and T. X. Wu. 2006. Meta-analysis of 5% imiquimod and 0.5% podophyllotoxin in the treatment of condylomata acuminata. Dermatology 213:218-223.