Document 2858
 DOCN  M94A2858
 TI    Non-nucleoside RT inhibitors with structural diversity but potent
       anti-HIV activity.
 DT    9412
 AU    Yang SS; Buckheit RW Jr; Bader JP; DTP, NCI, Bethesda, MD 20892.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):209 (abstract no. PB0264). Unique
       Identifier : AIDSLINE ICA10/94369717
 AB    Current thrust in controlling AIDS targets the infection and replication
       of the human immunodeficiency virus (HIV). To date treatment of AIDS has
       relied upon nucleoside reverse transcriptase (RT) inhibitors such as
       AZT, ddI, ddC, and ddA, which eventually become ineffective due to the
       emergence of HIV mutants bearing resistance to the specific nucleoside
       inhibitor, or because of intolerable toxicities. The National Cancer
       Institute conducts and coordinates a highly organized and systematic in
       vitro screening program on synthetic and natural compounds submitted by
       various individuals or institutions world-wide. Over 3000 active
       compounds were examined in a panel of laboratory and clinical strains of
       HIV, including certain drug-resistant strains, in cell lines or fresh
       human lymphocyte, macrophage/monocyte cell preparations. We were able to
       identify 8 categories and 17 other unique compounds that fit within the
       non-nucleoside RT inhibitor (NNRTI) group, based on their inhibition
       patterns against various HIV strains. These compounds also inhibited
       enzymatic RT when evaluated using heteropolymeric templates. When tested
       in combination with AZT, many of the NNRTI's exhibit synergistic
       inhibition of HIV-1, suggesting that combination antiviral therapy with
       AZT may be therapeutically promising for AIDS treatment. Several
       resistant HIV-1 strains were selected from cultures treated with one or
       another of the NNRTI's. The pattern of cross resistance among the
       compounds demonstrates that they are not identical with respect to
       interaction with the viral RT.
 DE    Antiviral Agents/*PHARMACOLOGY  Cell Line  Cells, Cultured  Drug
       Resistance  Drug Screening  Drug Synergism  Enzyme
       Inhibitors/CLASSIFICATION/PHARMACOLOGY  Human  HIV-1/*DRUG EFFECTS
       Lymphocytes/MICROBIOLOGY  National Institutes of Health (U.S.)
       Phagocytes/MICROBIOLOGY  Reverse Transcriptase/*ANTAGONISTS & INHIB
       United States  Zidovudine/PHARMACOLOGY  MEETING ABSTRACT

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