Document 0982
 DOCN  M9470982
 TI    Anti-angiogenesis agent DS-4152 is a potent and selective inhibitor of
       HIV-1 replication in vitro.
 DT    9409
 AU    Baba M; Shigeta S; Ikeuchi T; Korenaga H; Osada Y; Department of
       Microbiology, Fukushima Medical College, Japan.
 SO    AIDS. 1994 Jan;8(1):43-8. Unique Identifier : AIDSLINE MED/94280703
 AB    OBJECTIVE: To determine whether the anti-angiogenesis agent DS-4152
       inhibits the replication of HIV-1 in vitro. DESIGN: A sulfated
       polysaccharide-peptidoglycan DS-4152 has recently been identified as a
       potent and selective inhibitor of Kaposi's sarcoma (KS). Therefore, it
       is important to evaluate the anti-HIV-1 activity of DS-4152 alone and in
       combination with dideoxynucleosides. METHODS: Activity of DS-4152
       against HIV-1 replication was examined in MT-4, Molt-4, and peripheral
       blood lymphocyte cells. The inhibitory effect of the compound on
       syncytium-formation was determined by cocultivation of Molt-4 cells with
       Molt-4/IIIB cells. Inhibition of virus adsorption to the host cells was
       measured by a p24 antigen capture enzyme-linked immunosorbent assay.
       RESULTS: DS-4152 showed potent and selective inhibition of HIV-1
       replication in the cell systems. Its 50% effective concentration for
       HIV-1 (IIIB strain) in MT-4 cells was 0.7 microgram/ml. The compound was
       not cytotoxic at concentrations < or = 100 micrograms/ml. DS-4125 proved
       inhibitory to syncytium-formation and virus adsorption. The anti-HIV-1
       activities of zidovudine, dideoxycytidine and dideoxyinosine were not
       affected by the presence of DS-4152. CONCLUSION: DS-4152 has the
       potential, from these in vitro studies, to function as an anti-HIV-1 as
       well as an anti-angiogenesis agent. In order to determine this
       possibility, consequences of DS-4152 infusion on HIV-1 p24 serum levels
       and CD4+ cell counts over time are being examined in ongoing clinical
       trials in the United States on patients with AIDS-associated KS.
 DE    Antiviral Agents/*PHARMACOLOGY  Cell Line  Didanosine/PHARMACOLOGY
       Giant Cells/DRUG EFFECTS/MICROBIOLOGY  Human  HIV-1/*DRUG
       EFFECTS/PHYSIOLOGY  Neovascularization/DRUG THERAPY  Polysaccharides,
       Bacterial/*PHARMACOLOGY  Support, Non-U.S. Gov't  Virus
       Replication/*DRUG EFFECTS  Zalcitabine/PHARMACOLOGY  JOURNAL ARTICLE

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