Document 0001
 DOCN  M9470001
 TI    Competitive inhibition of HIV-1 protease by warfarin derivatives.
 DT    9409
 AU    Tummino PJ; Ferguson D; Hupe D; Department of Biochemistry, Parke-Davis
       Pharmaceutical Research,; Division of Warner-Lambert Company, Ann Arbor,
       Michigan 48105.
 SO    Biochem Biophys Res Commun. 1994 May 30;201(1):290-4. Unique Identifier
       : AIDSLINE MED/94256992
 AB    The oral anticoagulant warfarin (4-hydroxy-3-(3-oxo-1-phenylbutyl)-
       benzopyran-2-one) is a structurally novel low micromolar competitive
       inhibitor of HIV-1 protease in vitro. It was recently reported that
       warfarin inhibits HIV-1 infection in U-1 monocytes and viral production
       in ACH-2 lymphocytes (Bourinbaiar, A.S. et al., (1993) AIDS 7, 129-130).
       Our results demonstrate that warfarin and a series of structurally
       related analogs inhibit the viral protease, the most potent analog
       having an IC50 = 1.9 microM. Kinetic analysis reveals inhibition by
       warfarin occurs in a competitive manner, with Ki = 3.3 microM. While it
       is unclear whether the cellular inhibition previously reported is due to
       inhibition of HIV-1 protease, the warfarin analogs are a novel class of
       nonpeptide HIV-1 protease inhibitors.
 DE    *HIV Protease Inhibitors  Warfarin/*ANALOGS & DERIVATIVES/PHARMACOLOGY
       JOURNAL ARTICLE

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