Chokekijchai S, Shirasaka T, Weinstein J N, Mitsuya H
Experimental Retrovirology Section, National Cancer Institute, Bethesda, MD 20892, USA.
Antiviral Res. 1995 Sep;28(1):25-38. doi: 10.1016/0166-3542(95)00036-l.
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.
KNI-272是一种构象受限的人类免疫缺陷病毒（HIV）蛋白酶抑制剂，含有P1别苯基去甲亮氨酸（Apns）（(2S,3S)-3-氨基-2-羟基-4-苯基丁酸），已被证明在体外是多种HIV毒株复制的选择性强效抑制剂。当KNI-272与3'-叠氮基-2',3'-双脱氧胸苷（AZT）或2',3'-双脱氧肌苷（ddI）联合用于检测植物血凝素激活的外周血单核细胞（PHA-PBM）中的原发性HIV-1分离株时，经COMBO程序包分析，其活性为相加作用，而非协同或拮抗作用。当单独检测KNI-272在静息PBM（R-PBM）和PHA-PBM中的抗HIV-1活性时，发现其在两种靶细胞群体中对病毒的效力相当，而AZT在PHA-PBM中比在R-PBM中效力更强，ddI在R-PBM中效力更强。这些数据表明KNI-272及其类似物具有潜在的临床应用价值。
