Document 0089
 DOCN  M9440089
 TI    In vitro anti-human immunodeficiency virus (HIV) activity of XM323, a
       novel HIV protease inhibitor.
 DT    9404
 AU    Otto MJ; Reid CD; Garber S; Lam PY; Scarnati H; Bacheler LT; Rayner MM;
       Winslow DL; Du Pont Merck Pharmaceutical Company, Glenolden,
       Pennsylvania; 19036.
 SO    Antimicrob Agents Chemother. 1993 Dec;37(12):2606-11. Unique Identifier
       : AIDSLINE MED/94153034
 AB    XM323 represents a novel class of potent inhibitors of human
       immunodeficiency virus (HIV) protease. In vitro studies have shown that
       inhibition of this enzyme translates into potent inhibition of
       replication of HIV type 1 (HIV-1) and HIV-2. The inhibition of virus
       replication was assessed with three assays designed to measure the
       production of infectious virus, viral RNA, or p24 antigen. The
       production of mature infectious virions was measured with a yield
       reduction assay. By this assay, several strains and isolates of HIV-1
       and HIV-2 were shown to be susceptible to XM323 in two lymphoid cell
       lines (MT-2 and H9) and in normal peripheral blood mononuclear cells,
       with a concentration required for 90% inhibition (IC90) of 0.12 +/- 0.04
       microM (mean +/- standard deviation). The production of HIV-1(RF) RNA
       was measured with an RNA hybridization-capture assay. With this assay,
       XM323 was shown to be a potent inhibitor of HIV-1(RF) replication, with
       an IC90 of 0.063 +/- 0.032 microM. A third measure of virus replication,
       the production of p24 viral antigen, an essential protein component of
       the virion, was determined with the AIDS Clinical Trial Group-Department
       of Defense peripheral blood mononuclear cell consensus assay. This assay
       was used for expanded testing of XM323 against 28 clinical isolates and
       laboratory strains of HIV-1. XM323 was shown to be equally effective
       against zidovudine-susceptible and zidovudine-resistant isolates of
       HIV-1, with an overall IC90 of 0.16 +/- 0.06 microM.
 DE    Antiviral Agents/*PHARMACOLOGY  Azepines/*PHARMACOLOGY  Human  HIV/*DRUG
       EFFECTS/METABOLISM/PHYSIOLOGY  HIV Core Protein p24/BIOSYNTHESIS  HIV
       Protease Inhibitors/*PHARMACOLOGY  HIV-1/DRUG EFFECTS/ENZYMOLOGY
       HIV-2/DRUG EFFECTS/ENZYMOLOGY  Leukocytes, Mononuclear/DRUG
       EFFECTS/MICROBIOLOGY  Nucleic Acid Hybridization  RNA,
       Viral/ANALYSIS/BIOSYNTHESIS  Virus Replication/DRUG EFFECTS  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).