grl-98065 and HIV-Infections

grl-98065 has been researched along with HIV-Infections* in 2 studies

Reviews

1 review(s) available for grl-98065 and HIV-Infections

ArticleYear
Harnessing nature's insight: design of aspartyl protease inhibitors from treatment of drug-resistant HIV to Alzheimer's disease.
    Journal of medicinal chemistry, 2009, Apr-23, Volume: 52, Issue:8

    Topics: Alzheimer Disease; Amyloid Precursor Protein Secretases; Animals; Antiviral Agents; Aspartic Acid Endopeptidases; Biological Products; Darunavir; Drug Design; Drug Discovery; Drug Resistance, Viral; Enzyme Inhibitors; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Molecular Mimicry; Molecular Structure; Peptides; Structure-Activity Relationship; Sulfonamides

2009

Other Studies

1 other study(ies) available for grl-98065 and HIV-Infections

ArticleYear
A novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI), GRL-98065, is potent against multiple-PI-resistant human immunodeficiency virus in vitro.
    Antimicrobial agents and chemotherapy, 2007, Volume: 51, Issue:6

    We designed, synthesized, and identified GRL-98065, a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing the structure-based designed privileged cyclic ether-derived nonpeptide P2 ligand, 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF), and a sulfonamide isostere, which is highly potent against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC(50)], 0.0002 to 0.0005 microM) with minimal cytotoxicity (50% cytotoxicity, 35.7 microM in CD4(+) MT-2 cells). GRL-98065 blocked the infectivity and replication of each of the HIV-1(NL4-3) variants exposed to and selected by up to a 5 microM concentration of saquinavir, indinavir, nelfinavir, or ritonavir and a 1 microM concentration of lopinavir or atazanavir (EC(50), 0.0015 to 0.0075 microM), although it was less active against HIV-1(NL4-3) selected by amprenavir (EC(50), 0.032 microM). GRL-98065 was also potent against multiple-PI-resistant clinical HIV-1 variants isolated from patients who had no response to existing antiviral regimens after having received a variety of antiviral agents, HIV-1 isolates of various subtypes, and HIV-2 isolates examined. Structural analyses revealed that the close contact of GRL-98065 with the main chain of the protease active-site amino acids (Asp29 and Asp30) is important for its potency and wide-spectrum activity against multiple-PI-resistant HIV-1 variants. The present data demonstrate that the privileged nonpeptide P2 ligand, bis-THF, is critical for the binding of GRL-98065 to the HIV protease substrate binding site and that this scaffold can confer highly potent antiviral activity against a wide spectrum of HIV isolates.

    Topics: Amino Acid Sequence; Drug Design; Drug Resistance, Multiple, Viral; Furans; HIV Infections; HIV Protease; HIV Protease Inhibitors; HIV-1; Humans; Inhibitory Concentration 50; Microbial Sensitivity Tests; Models, Molecular; Molecular Sequence Data; Sulfonamides; Urethane; Virus Replication

2007