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

被引：784

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

[1] EVOLUTION OF TYPE-C VIRAL GENES - ORIGIN OF FELINE LEUKEMIA-VIRUS [J].

BENVENISTE, RE ;

SHERR, CJ ;

TODARO, GJ .

SCIENCE, 1975, 190 (4217) :886-888

[2] RAPID COLORIMETRIC ASSAY FOR CELL-GROWTH AND SURVIVAL - MODIFICATIONS TO THE TETRAZOLIUM DYE PROCEDURE GIVING IMPROVED SENSITIVITY AND RELIABILITY [J].

DENIZOT, F ;

LANG, R .

JOURNAL OF IMMUNOLOGICAL METHODS, 1986, 89 (02) :271-277

[3] DETAILED MODEL OF REVERSE TRANSCRIPTION AND TESTS OF CRUCIAL ASPECTS [J].

GILBOA, E ;

MITRA, SW ;

GOFF, S ;

BALTIMORE, D .

CELL, 1979, 18 (01) :93-100

[4]

HO DD, 1989, NEW ENGL J MED, V321, P1622

[5] KINETICS OF PHARMACOLOGIC RESPONSE [J].

HOLFORD, NHG ;

SHEINER, LB .

PHARMACOLOGY & THERAPEUTICS, 1982, 16 (02) :143-166

[6] HIV WITH REDUCED SENSITIVITY TO ZIDOVUDINE (AZT) ISOLATED DURING PROLONGED THERAPY [J].

LARDER, BA ;

DARBY, G ;

RICHMAN, DD .

SCIENCE, 1989, 243 (4899) :1731-1734

[7]

MAJUMDAR C, 1988, J BIOL CHEM, V263, P15657

[8]

MERLUZZI VJ, UNPUB

[9] 3'-AZIDO-3'-DEOXYTHYMIDINE (BW A509U) - AN ANTIVIRAL AGENT THAT INHIBITS THE INFECTIVITY AND CYTOPATHIC EFFECT OF HUMAN LYMPHOTROPIC-T VIRUS TYPE-III LYMPHADENOPATHY-ASSOCIATED VIRUS INVITRO [J].

MITSUYA, H ;

WEINHOLD, KJ ;

FURMAN, PA ;

STCLAIR, MH ;

LEHRMAN, SN ;

GALLO, RC ;

BOLOGNESI, D ;

BARRY, DW ;

BRODER, S .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (20) :7096-7100

[10] RECOMBINANT HIV-1 REVERSE-TRANSCRIPTASE - PURIFICATION, PRIMARY STRUCTURE, AND POLYMERASE RIBONUCLEASE-H ACTIVITIES [J].

MIZRAHI, V ;

LAZARUS, GM ;

MILES, LM ;

MEYERS, CA ;

DEBOUCK, C .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1989, 273 (02) :347-358

← 1 2 3 →