Viracept (Nelfinavir Mesylate, AG1343): A Potent, Orally Bioavailable Inhibitor of HIV-1 Protease
Citations Over TimeTop 10% of 1997 papers
Abstract
Using a combination of iterative structure-based design and an analysis of oral pharmacokinetics and antiviral activity, AG1343 (Viracept, nelfinavir mesylate), a nonpeptidic inhibitor of HIV-1 protease, was identified. AG1343 is a potent enzyme inhibitor (Ki = 2 nM) and antiviral agent (HIV-1 ED50 = 14 nM). An X-ray cocrystal structure of the enzyme-AG1343 complex reveals how the novel thiophenyl ether and phenol-amide substituents of the inhibitor interact with the S1 and S2 subsites of HIV-1 protease, respectively. In vivo studies indicate that AG1343 is well absorbed orally in a variety of species and possesses favorable pharmacokinetic properties in humans. AG1343 (Viracept) has recently been approved for marketing for the treatment of AIDS.
Related Papers
- → Human Immunodeficiency Virus Type 1 Protease Genotypes and In Vitro Protease Inhibitor Susceptibilities of Isolates from Individuals Who Were Switched to Other Protease Inhibitors after Long-Term Saquinavir Treatment(1998)102 cited
- → Activity of the Combination of Nelfinavir and Saquinavir against Human Immunodeficiency Virus after Failure of Prior Protease Inhibitor Therapy(1999)10 cited
- Protease inhibitors: resistance, resistance, resistance.(1997)
- HIV-1 protease inhibitor nelfinavir decreases insulin secretion from rat insulinoma INS-1 cells(2004)
- Another protease inhibitor proves highly effective.(1996)