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Titolo:
Perspectives of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the therapy of HIV-1 infection
Autore:
De Clercq, E;
Indirizzi:
Catholic Univ Louvain, Rega Inst Med Res, B-3000 Louvain, Belgium CatholicUniv Louvain Louvain Belgium B-3000 es, B-3000 Louvain, Belgium
Titolo Testata:
FARMACO
fascicolo: 1-2, volume: 54, anno: 1999,
pagine: 26 - 45
SICI:
0014-827X(199901/02)54:1-2<26:PONRTI>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS TYPE-1; HIGH-DOSE NEVIRAPINE; NONNUCLEOSIDE INHIBITORS; ANTIVIRAL ACTIVITY; ANTI-HIV-1 ACTIVITY; IN-VITRO; 1-<(2-HYDROXYETHOXY)METHYL>-6-(PHENYLTHIO)THYMINE DERIVATIVES; SYNERGISTIC INHIBITION; PYRIDINONE DERIVATIVES; SELECTIVE-INHIBITION;
Keywords:
NNRTIs (non-nucleoside reverse transcriptase inhibitors; nevirapine; delavirdine; reverse transcriptase; HIV; triple-drug combinations;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
157
Recensione:
Indirizzi per estratti:
Indirizzo: De Clercq, E Catholicain,v Louvain, Rega Inst Med Res, Minderbroedersstr 10, B-3000 Louv Catholic Univ Louvain Minderbroedersstr 10 Louvain Belgium B-3000
Citazione:
E. De Clercq, "Perspectives of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the therapy of HIV-1 infection", FARMACO, 54(1-2), 1999, pp. 26-45

Abstract

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have, in additionto the nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), gained a definitive place in the treatment of HIV-1 infections. Starting from the HEPT and TIBO derivatives, more than thirty structurally different classes of compounds have been identified as NNRTIs, that iscompounds that are specifically inhibitory to HIV-1 replication and targeted at the HIV-1 reverse transcriptase (RT). Two NNRTIs (nevirapine and delavirdine) have been formally licensed for clinical use and several others are (or have been) in preclinical and/or clinical development [tivirapine (TIBO R-86183), loviride (alpha-APA R89439), thiocarboxanilide UC-781, HEPT derivative MKC-442, quinoxaline HEY 097, DMP 266 (efavirenz), PETT derivatives (trovirdine, PETT-4, PETT-5) and the dichlorophenylthio(pyridyl)imidazolederivative S-1153]. The NNRTIs interact with a specific 'pocket' site of HIV-1 RT that is closely associated with, but distinct from, the NRTI binding site. NNRTIs are notorious for rapidly eliciting resistance due to mutations of the amino acids surrounding the NNRTI-binding site. However, the emergence of resistant HIV strains can be circumvented if the NNRTIs, preferably in combination with other anti-HIV agents, are used from the start at sufficiently high concentrations. In vitro, this procedure has been shown to 'knock-out' virus replication and to prevent resistance from arising. In vivo, various triple-drug combinations containing NNRTIs, NRTIs and/or PIs may result in an effective viral suppression and ensuing immune recovery. However, this so-called HAART (highly active antiretroviral therapy) may also fail, and this necessitates the design of new and more effective drugs and drug cocktails. (C) 1999 Elsevier Science S.A. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/09/20 alle ore 09:37:05