title: In vitro anti-HIV-1 activity of HIV protease inhibitor KNI-272 in resting and activated cells: implications for its combined use with AZT or ddI.
abstract: KNI-272, a conformationally constrained human immunodeficiency virus (HIV) protease inhibitor containing a P1 allophenylnorstatine (Apns) ((2S,3S)- 3-amino-2-hydroxy-4-phenylbutyric acid), has been shown to be a selective and potent inhibitor of the replication of a wide spectrum of HIV strains in vitro. When KNI-272 was tested in combination with 3'-azido-2',3'-dideoxythymidine (AZT) or 2',3'-dideoxyinosine (ddI) against a primary HIV-1 isolate in phytohemagglutin-activated peripheral blood mononuclear cells (PHA-PBM), its activity was identified to be additive, but not synergistic or antagonistic, as analyzed with the COMBO program package. When tested alone for anti-HIV-1 activity in resting PBM (R-PBM) and PHA-PBM, KNI-272 was found to be comparably potent against the virus in both target cell populations, whereas AZT was more potent in PHA-PBM than in R-PBM and ddI was more potent in R-PBM. These data suggest a potential clinical application of KNI-272 and its analogs.
authors.affiliation: Experimental Retrovirology Section, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chokekijchai
authors.forename: T
authors.initials: T
authors.lastname: Shirasaka
authors.forename: J N
authors.initials: JN
authors.lastname: Weinstein
authors.forename: H
authors.initials: H
authors.lastname: Mitsuya
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016049:Didanosine / Q000494:pharmacology*; D004347:Drug Interactions; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D015394:Molecular Structure; D009842:Oligopeptides / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D010835:Phytohemagglutinins; D015215:Zidovudine; D016049:Didanosine; C077822:kynostatin 272