Linked Life Data

15080937

Source:http://linkedlifedata.com/resource/pubmed/id/15080937

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2004-4-14
pubmed:abstractText
Epidermal growth factor receptor (EGFR) protein tyrosine kinases (PTKs) are attractive targets for anti-tumor drug design. Although thousands of their ligands have been studied as potential inhibitors against PTKs, there is no QSAR study that covers different kinds of inhibitors with observable structural diversity. However, by using this approach, we could mine far more useful information. Hence in order to better understand the binding model and the relationship between the physicochemical properties and the inhibitory activities of different kind of various inhibitors, molecular docking and 3D-QSAR, viz. CoMFA and CoMSIA, were combined to study 124 reported inhibitors with different scaffolds. Based on the docked binding conformations, highly reliable and predictive 3D-QSAR models were derived, which reveal how steric, electrostatic, and hydrophobic interactions contribute to inhibitors' bioactivities. This result also demonstrates that it is possible to include different kinds of inhibitors with observable structural diversity into one 3D-QSAR study. Therefore, this study not only casts light on binding mechanism between EGFR and its inhibitors, but also provides new hints for de novo design of new EGFR inhibitors with observable structural diversity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0968-0896
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2409-17
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Elucidating inhibitory models of the inhibitors of epidermal growth factor receptor by docking and 3D-QSAR.
pubmed:affiliation
Drug Discovery & Design Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't