Linked Life Data

16432877

Source:http://linkedlifedata.com/resource/pubmed/id/16432877

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-2-7
pubmed:abstractText
A topological substructural molecular design approach (TOPS-MODE) has been used to predict whether a given compound is a P-glycoprotein (P-gp) substrate or not. A linear discriminant model was developed to classify a data set of 163 compounds as substrates or nonsubstrates (91 substrates and 72 nonsubstrates). The final model fit the data with sensitivity of 82.42% and specificity of 79.17%, for a final accuracy of 80.98%. The model was validated through the use of an external validation set (40 compounds, 22 substrates and 18 nonsubstrates) with a 77.50% of prediction accuracy; fivefold full cross-validation (removing 40 compounds in each cycle, 80.50% of good prediction) and the prediction of an external test set of marketed drugs (35 compounds, 71.43% of good prediction). This methodology evidenced that the standard bond distance, the polarizability and the Gasteiger-Marsilli atomic charge affect the interaction with the P-gp; suggesting the capacity of the TOPS-MODE descriptors to estimate the P-gp substrates for new drug candidates. The potentiality of the TOPS-MODE approach was assessed with a family of compounds not covered by the original training set (6-fluoroquinolones), and the final prediction had a 77.7% of accuracy. Finally, the positive and negative substructural contributions to the classification of 6-fluoroquinolones, as P-gp substrates, were identified; evidencing the possibilities of the present approach in the lead generation and optimization processes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3549
pubmed:author
pubmed:copyrightInfo
Copyright 2006 Wiley-Liss, Inc. and the American Pharmacists Association.
pubmed:issnType
Print
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
589-606
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
A topological substructural approach for the prediction of P-glycoprotein substrates.
pubmed:affiliation
Department of Drug Design, Centre of Chemical Bioactive, Central University of Las Villas, Santa Clara, Villa Clara, Cuba. macabrera@cbq.uclv.edu.cu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't