sc-52151 and kynostatin-272

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.

Topics: Animals; Blood Proteins; CD4 Lymphocyte Count; Clinical Trials as Topic; Drug Industry; Drug Resistance; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Humans; Isoquinolines; Oligopeptides; Protein Binding; Pyrones; Quinolines; Rats; Saquinavir; Technology, Pharmaceutical; Urea; Warfarin; Zidovudine