Linked Life Data

21047106

Source:http://linkedlifedata.com/resource/pubmed/id/21047106

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2010-11-22
pubmed:abstractText
The NK(3) subtype of tachykinin receptor is a G protein-coupled receptor that is a potential therapeutic target for several neurological diseases, including schizophrenia. In this study, we have screened compound databases for novel NK(3) receptor antagonists using a virtual screening protocol of similarity analysis. The lead compound for this study was the potent NK(3) antagonist talnetant. Compounds of the quinoline type found in the virtual screen were additionally evaluated in a comparative molecular field analysis model to predict activity a priori to testing in vitro. Selected members of this latter set were tested for their ability to inhibit ligand binding to the NK(3) receptor as well as to inhibit senktide-induced calcium responses in cells expressing the human NK(3) receptor. Two novel compounds were identified that inhibited NK(3) receptor agonist binding, with potencies in the nM range and antagonized NK(3) receptor-mediated increases in intracellular calcium. These results demonstrate the utility of similarity analysis in identifying novel antagonist ligands for neuropeptide receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
25
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8080-8
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Virtual screening to identify novel antagonists for the G protein-coupled NK3 receptor.
pubmed:affiliation
Department of Pharmaceutical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, Ohio 44272, USA.
pubmed:publicationType
Journal Article