INHIBITION OF HIV-1 REPLICATION BY A NONNUCLEOSIDE REVERSE-TRANSCRIPTASE INHIBITOR

被引：781

作者：

MERLUZZI, VJ ^{[1
]}

HARGRAVE, KD ^{[1
]}

LABADIA, M ^{[1
]}

GROZINGER, K ^{[1
]}

SKOOG, M ^{[1
]}

WU, JC ^{[1
]}

SHIH, CK ^{[1
]}

ECKNER, K ^{[1
]}

HATTOX, S ^{[1
]}

ADAMS, J ^{[1
]}

ROSEHTHAL, AS ^{[1
]}

FAANES, R ^{[1
]}

ECKNER, RJ ^{[1
]}

KOUP, RA ^{[1
]}

SULLIVAN, JL ^{[1
]}

机构：

[1] UNIV MASSACHUSETTS,SCH MED,DEPT PEDIAT & MED,PROGRAM MOLEC MED,WORCESTER,MA 01605

来源：

SCIENCE | 1990年 / 250卷 / 4986期

关键词：

D O I：

10.1126/science.1701568

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A series of dipyridodiazepinones have been shown to be potent inhibitors of human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT). One compound, BI-RG-587, had a Ki of 200 nanomolar for inhibition of HIV-1 RT that was noncompetitive with respect to deoxyguanosine triphosphate. BI-RG-587 was specific for HIV-1 RT, having no effect on feline and simian RT or any mammalian DNA polymerases. BI-RG-587 inhibited HIV-1 replication in vitro as demonstrated by in situ hybridization, inhibition of protein p24 production, and the lack of syncytia formation in cultured human T cell lines and freshly isolated human peripheral blood lymphocytes. Cytotoxicity studies of BI-RG-587 on human cells showed a high therapeutic index (>8000) in culture.

引用

页码：1411 / 1413

页数：3

共 23 条

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