Document 2238
 DOCN  M94A2238
 TI    SDZ SID 791 (JM 3100): a mechanistically unique anti-HIV agent with
       potent antiviral activity in vitro and in vivo.
 DT    9412
 AU    Datema R; Sandoz Research Institute, Vienna, Austria.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):35 (abstract no. 113A). Unique
       Identifier : AIDSLINE ICA10/94370337
 AB    OBJECTIVE: To determine whether SID 791 has a potential as an anti-HIV
       agent. RESULTS: SID 791 is a bicyclam blocking HIV replication in vitro
       (including that of various clinical isolates in primary T-cells and
       monocytes) by > 90% at concentrations of 1-10 nM. The in vitro
       selectivity index is > 300,000. SID 791 blocks an uncoating/fusion step
       in acute infections and--in chronically infected cells--the infectivity
       of released particles. Decreased sensitivity of HIV-1, NL4.3, to the
       compound develops slowly upon serial passaging in vitro (50 passages for
       100-fold increase in IC50). In rats SID 791 has a long terminal
       half-life (53h from blood cells) and a large volume of distribution. The
       bicyclam binds to plasma proteins, but this does not effect its
       antiviral activity. At non-toxic, once-daily, subcutaneous doses of > 1
       mg/kg/day, SID 791 suppresses HIV-1 replication in intrathymically
       infected SCID-hu (Thy/Liv) mice. CONCLUSION: The properties of SID 791
       suggest a potential for antiviral therapy.
 DE    Animal  Antiviral Agents/*PHARMACOLOGY/PHARMACOKINETICS  Bicyclo
       Compounds/PHARMACOLOGY  Half-Life  HIV/*DRUG EFFECTS/PHYSIOLOGY
       HIV-1/DRUG EFFECTS  In Vitro  Mice  Mice, Inbred Strains  Protein
       Binding  Rats  Virus Replication/*DRUG EFFECTS  MEETING ABSTRACT

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