MKC-442. Non-nucleoside reverse transcriptase inhibitor

Drugs of the Future

Volumn 23, Issue 7, 1998, Pages 718-724

  Furman, Phillip A ^a   Moxham, Cary ^a  

^a Triangle Pharmaceuticals   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; DIDANOSINE; EMIVIRINE; LAMIVUDINE; NEVIRAPINE; RNA DIRECTED DNA POLYMERASE INHIBITOR; SAQUINAVIR; ZALCITABINE; ZIDOVUDINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG POTENTIATION; DRUG STRUCTURE; FEMALE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MALE; NONHUMAN; ORAL DRUG ADMINISTRATION; PHASE 1 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; RAT; VIRUS INHIBITION;

EID: 0031715563     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.1998.023.07.466749     Document Type: Article

References (19)

1. Baba, M., Tanaka, H., Miyasaka, T., Yuasa, S., Ubasawa, M., Walker, R.T., De Clercq, E. HEPT derivatives: 6-Benzyl-1-ethoxymethyl-5-isopropyluracil (MKC-442). Nucleosides Nucleotides 1995, 14: 575-83.
2. Miyasaka, T., Tanaka, H., Baba, M., Hayakawa, H., Walker, R.T., Balzarini, J., De Clercq, E. A novel lead for specific anti-HIV-1 agents: 1-[(2-Hydroxyethoxy)-methyl]-6-(phenylthio)thymidine. J Med Chem 1989, 32: 2507-9.
3. Baba, M., Tanaka, H., De Clercq, E., Pauwels, R., Balzarini, J., Schols, D., Nakashima, H., Perno, C.-F., Walker, R.T., Miyasaka, T. Highly specific inhibition of human immunodeficiency virus type 1 by a novel 6-substituted acyclouridine derivative. Biochem Biophys Res Commun 1989, 165: 1375-81.
4. Yuasa, S., Sadakata, Y., Takashima, H., Sekiya, K., Inouye, N., Ubasawa, M., Baba, M. Selective and synergistic inhibition of human immunodeficiency virus type 1 reverse transcriptase by a non-nucleoside inhibitor, MKC-442. Mol Pharmacol 1993, 44: 895-900.
5. Hopkins, A.L., Ren, J., Esnouf, R.M. et al. Complexes of HIV-1 reverse transcriptase with inhibitors of the HEPT series reveal conformational changes relevant to the design of potent non-nucleoside inhibitors. J Med Chem 1996, 39: 1589-600.
6. Brennan, T.M., Taylor, D.L., Bridges, C.G., Leyda, J.P., Tymps, A.S. The inhibition of human immunodeficiency virus type 1 in vitro by a non-nucleoside reverse transcriptase inhibitor MKC-442, alone and in combination with other anti-HIV compounds. Antivir Res 1995, 26: 173-87.
7. Baba, M., Shigeta, S., Yuasa, S., Takashima, H., Sekiya, K., Ubasawa, M., Tanaka, H., Miyasaka, T., Walker, R.T., De Clercq, E. Preclinical evaluation of MKC-442, a highly potent and specific inhibitor of human immunodeficiency virus type 1 in vitro. Antimicrob Agents Chemother 1994, 38: 688-92.
8. Seki, M., Sadakata, Y., Yuasa, S., Baba, M. Isolation and characterization of human immunodeficiency virus type 1 mutants resistant to the non-nucleotide reverse transcriptase inhibitor MKC-442. Antivir Chem Chemother 1995, 6: 73-9.
9. Piras, G., Nakade, K., Yuasa, S., Baba, M. Three-drug combination of MKC-442, lamivudine, and zidovudine in vitro: Potential approach towards effective chemotherapy against HIV-1. AIDS 1997, 11: 469-75.
10. Balzarini, J., Pelemans, H., Pérez-Pérez, M.-J., San Felix, A., Camarasa, M.-J., De Clercq, E., Karlsson, A. Marked inhibitory activity of non-nucleoside reverse transcriptase inhibitors against human immunodeficiency virus type 1 when combined with (-) 2′,3′-dideoxy-3′-thiacytidine. Mol Pharmacol 1996, 49: 882-90.
11. Okamoto, M., Makino, M., Yamada, K., Nakade, K., Yuasa, S., Baba, M. Complete inhibition of viral breakthrough by combination of MKC-442 with AZT during a long-term culture of HIV-1-infected cells. Antivir Res 1996, 31: 69-77.
12. Richman, D.D., Havlir, D., Corbeil, J. et al. Nevirapine resistance mutations of human immunodeficiency virus type 1 selected during therapy. J Virol 1994, 68: 1660-6.
13. Furman, P., Barry, D.W., Borroto-Esoda, K. et al. Preclinical development of MKC-442, a potent and selective non-nucleoside inhibitor of HIV reverse transcriptase. 4th Conf Retrovir Opportunistic Infect (Jan 22-26, Washington DC) 1997, Poster 571.
14. Szczech, G.M., Furman, P., Painter, G.R. et al. Safety assessment, in vitro and in vivo, and pharmacokinetics of MKC-442, a potent and selective non-nucleoside reverse transcriptase inhibitor of HIV-1. Antimicrob Agents Chemother. Submitted for publication.
15. Pialoux, G., Fournier, S., Moulignier, A., Poveda, J.-D., Clavel, F., Dupont, B. Central nervous system as a sanctuary for HIV-1 infection despite treatment with zidovudine, lamivudine and indinavir. AIDS 1997, 11: 1302-3.
16. Baba, M., Yuasa, S., Niwa, T. et al. Effect of human serum on the in vitro anti-HIV-1 activity of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymidine (HEPT) derivatives as related to their lipophilicity and serum protein binding. Biochem Pharmacol 1993, 45: 2507-12.
17. Moxham, C.P., Szczech, G.M., Blum, M.R., Barry, D.W. Pharmacokinetics (PK) and safety of single escalating doses of MKC-442 in HIV-infected volunteers. 4th Conf Retrovir Opportunistic Infect (Jan 22-26, Washington DC) 1997, Poster 573.
18. Kimpton, J., Emerman, M. Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated β-galactosidase gene. J Virol 1992, 66: 2232-9.
19. Hill, E., Taylor, N., Borroto-Esoda, K., Furman, P., Moxham, C., Painter, G. In vitro synergy studies with MKC-442, a non-nucleoside HIV-1 reverse transcriptase inhibitor. 11th Int Conf Antiviral Res (Apr 5-10, San Diego) 1998, Poster 49.