2. Academic Validation
  3. Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease

Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease

  • J Med Chem. 1997 Nov 21;40(24):3979-85. doi: 10.1021/jm9704098.
S W Kaldor 1,  V J Kalish,  J F Davies 2nd,  B V Shetty,  J E Fritz,  K Appelt,  J A Burgess,  K M Campanale,  N Y Chirgadze,  D K Clawson,  B A Dressman,  S D Hatch,  D A Khalil,  M B Kosa,  P P Lubbehusen,  M A Muesing,  A K Patick,  S H Reich,  K S Su,  J H Tatlock
Affiliations

Affiliation

  • 1 Agouron Pharmaceuticals, Inc., San Diego, California 92121, USA.
PMID: 9397180 DOI: 10.1021/jm9704098
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.

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