Linked Life Data

7683360

Source:http://linkedlifedata.com/resource/pubmed/id/7683360

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1993-6-3
pubmed:abstractText
The TIBO, HEPT, nevirapine, pyridinone, BHAP, TSAO, and alpha-APA derivatives, although belonging to structurally diverging classes of molecules, share remarkable common features. They are specifically active against the reverse transcriptase of HIV-1 (TIBO and HEPT also, to a certain extent, against the reverse transcriptase of SIVagm strains), but not against the reverse transcriptases of HIV-2 or any other retroviruses. Nor are they active against any of the cellular DNA polymerases. These HIV-1-specific RT inhibitors seem to interact with a specific target site (YQYMDDLY) at positions 181-188, which is distinct from, but functionally and spatially related to, the substrate (dNTP) binding site. The tyrosine residues Y181 and Y188 play a crucial role in the interaction of TIBO and its congeners with their target site. The HIV-1-specific RT inhibitors have proven to inhibit the replication of various HIV-1 strains, including AZT-resistant HIV-1 strains, in different cell culture systems, including peripheral blood lymphocytes and monocyte/macrophages. In vitro they exhibit selectivity indexes of up to 5 orders of magnitude, which means that they are inhibitory to virus replication in cell culture at concentrations that are up to 100,000 times lower than the concentrations at which they are toxic to the host cells. As a rule, the HIV-1-specific RT inhibitors are orally bioavailable, as has been demonstrated with the TIBO and HEPT derivatives, nevirapine, pyridinones, and the alpha-APA derivatives in rats, dogs, monkeys, and humans. They sustain plasma drug levels that are well above the concentration required to inhibit virus replication in cell culture. Clinical studies have been undertaken with TIBO R82913, nevirapine, and pyridinones, and others (i.e., alpha-APA R89439) will soon follow. The problem of virus-drug resistance, which seems to readily emerge in vitro, will have to be addressed in the in vivo studies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0198-6325
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
229-58
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
HIV-1-specific RT inhibitors: highly selective inhibitors of human immunodeficiency virus type 1 that are specifically targeted at the viral reverse transcriptase.
pubmed:affiliation
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't