Protease inhibitors: where are they now?

GMHC Treat Issues. 1995 Jan;9(1):1-7.

Abstract

AIDS: Protease inhibitors block HIV by binding with its protease enzyme and it is hoped that they will be more potent and less toxic than nucleoside analogs. The companies Hoffmann-La Roche, Merck, Abbott, Searle, Agouron, Kyoto and Upjohn all have tested protease inhibitors in human trials. The drugs include L-524, ABT-538, AG- 1343, saquinavir, SC-52151, and SC-55389a. The protease inhibitors from Merck, Roche, and Abbott have shown higher anti-viral activity than any previous anti-HIV drug. Vertex, Burroughs Wellcome, and Kissei have conducted animal studies of VX-478, which shows promise in inhibiting the virus, with no toxicity. Other companies developing protease inhibitors include DuPont-Merck, Ciba-Geigy, Hoechst-Bayer, Nippon Mining, Parke-Davis, and Smith-Kline Beecham. Companies increasingly are combining protease inhibitors with nucleoside analogs, mainly AZT, in their large-scale efficacy studies in an effort to produce a strong and sustained anti-HIV effect. Potential cross-resistance to many of these compounds remains a major research issue. It is likely that at least one of the three leading companies in the field -- Merck, Abbott, or Roche -- will file for Food and Drug Administration approval in 1995. The National Drug Development Task Force is expected to announce the creation of a new task force on protease inhibitors.

Publication types

  • Newspaper Article

MeSH terms

  • Animals
  • Blood Proteins / metabolism
  • CD4 Lymphocyte Count / drug effects
  • Clinical Trials as Topic
  • Drug Industry
  • Drug Resistance
  • Drug Therapy, Combination
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / enzymology
  • HIV Protease Inhibitors / metabolism
  • HIV Protease Inhibitors / pharmacology
  • HIV Protease Inhibitors / therapeutic use*
  • Humans
  • Isoquinolines / administration & dosage
  • Isoquinolines / therapeutic use*
  • Oligopeptides / pharmacology
  • Oligopeptides / therapeutic use
  • Protein Binding
  • Pyrones / chemistry
  • Pyrones / pharmacology
  • Pyrones / therapeutic use
  • Quinolines / administration & dosage
  • Quinolines / therapeutic use*
  • Rats
  • Saquinavir
  • Technology, Pharmaceutical
  • Urea / analogs & derivatives
  • Urea / metabolism
  • Urea / pharmacology
  • Warfarin / pharmacology
  • Zidovudine / administration & dosage
  • Zidovudine / therapeutic use

Substances

  • Blood Proteins
  • HIV Protease Inhibitors
  • Isoquinolines
  • Oligopeptides
  • Pyrones
  • Quinolines
  • U 96988
  • Zidovudine
  • Warfarin
  • Urea
  • SC 52151
  • Saquinavir
  • kynostatin 272