| Autor: |
Robinson BS; Department of Virology and Non-Clinical Biostatistics, Bristol-Myers Squibb Company, Wallingford, Connecticut 06492, USA., Riccardi KA, Gong YF, Guo Q, Stock DA, Blair WS, Terry BJ, Deminie CA, Djang F, Colonno RJ, Lin PF |
| Jazyk: |
angličtina |
| Zdroj: |
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2000 Aug; Vol. 44 (8), pp. 2093-9. |
| DOI: |
10.1128/AAC.44.8.2093-2099.2000 |
| Abstrakt: |
BMS-232632 is an azapeptide human immunodeficiency virus type 1 (HIV-1) protease (Prt) inhibitor that exhibits potent anti-HIV activity with a 50% effective concentration (EC(50)) of 2.6 to 5.3 nM and an EC(90) of 9 to 15 nM in cell culture. Proof-of-principle studies indicate that BMS-232632 blocks the cleavage of viral precursor proteins in HIV-infected cells, proving that it functions as an HIV Prt inhibitor. Comparative studies showed that BMS-232632 is generally more potent than the five currently approved HIV-1 Prt inhibitors. Furthermore, BMS-232632 is highly selective for HIV-1 Prt and exhibits cytotoxicity only at concentrations 6,500- to 23, 000-fold higher than that required for anti-HIV activity. To assess the potential of this inhibitor when used in combination with other antiretrovirals, BMS-232632 was evaluated for anti-HIV activity in two-drug combination studies. Combinations of BMS-232632 with either stavudine, didanosine, lamivudine, zidovudine, nelfinavir, indinavir, ritonavir, saquinavir, or amprenavir in HIV-infected peripheral blood mononuclear cells yielded additive to moderately synergistic antiviral effects. Importantly, combinations of drug pairs did not result in antagonistic anti-HIV activity or enhanced cytotoxic effects at the highest concentrations used for antiviral evaluation. Our results suggest that BMS-232632 may be an effective HIV-1 inhibitor that may be utilized in a variety of different drug combinations. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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