Linked Life Data

18311908

Source:http://linkedlifedata.com/resource/pubmed/id/18311908

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-3-21
pubmed:abstractText
Type II cytochrome P450 (CYP) ligands cause inhibition by direct coordination to the heme iron atom. This interaction usually leads to high inhibitory potential, which can cause drug-drug interaction. The approach to design compounds with diminished CYP inhibition is different depending on whether the compound binds (type II ligand) or not (type I ligand) to the iron atom of the heme group. In this study, the structural characteristics of nitrogen-containing compounds, which bind to the iron atom in two CYP isoforms (CYP2C9 and CYP3A4), were investigated. The in vitro assays applied were fluorescence inhibition assay, difference spectra measurements, and K s determination. Computational modeling as an alternative method to difference spectra measurements to distinguish between type I and type II ligands was also explored. Since two CYP isoforms were used, information about the isoform specificity of type II ligands was also analyzed. The in silico method developed in this study applied together with the information gained from the experimental measurements may result in better decisions during the drug discovery process.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1755-63
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Characterization of type II ligands in CYP2C9 and CYP3A4.
pubmed:affiliation
Discovery DMPK and Bioanalytical Chemistry, AstraZeneca R&D Mölndal, Mölndal, Sweden. marie.m.ahlstrom@astrazeneca.com
pubmed:publicationType
Journal Article