Document Detail


The identification of neurotensin NTS1 receptor partial agonists through a ligand-based virtual screening approach.
MedLine Citation:
PMID:  18849166     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We identified small molecule NTS1R agonist compounds through virtual screening of the corporate database using a ROCS approach that searches multi-conformer representations efficiently. As a starting point for the ROCS search, we used the known NTS1R selective antagonist, SR-48527, based on the hypothesis that NT agonists and antagonists might share similar binding regions. Conformations were expanded and selected as database search queries based on a cluster analysis. The search provided us with virtual hits that were tested in intracellular calcium mobilization assays of NTS1R agonist and antagonist activities measured in FLIPR format as well as in [(3)H]NT competition binding studies. The results indicated that two initial hits produced partial agonist activity with potency in the moderate micromolar range.
Authors:
Yi Fan; Margaret H Lai; Kelly Sullivan; Michael Popiolek; Terrance H Andree; Paul Dollings; Mark H Pausch
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Publication Detail:
Type:  Journal Article     Date:  2008-09-24
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  18     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2009-10-30     Completed Date:  2009-12-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  5789-91     Citation Subset:  IM    
Affiliation:
Chemical & Screening Sciences, Wyeth Research, Princeton, NJ 08543, USA.fank@wyeth.com
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MeSH Terms
Descriptor/Qualifier:
Animals
CHO Cells
Cricetinae
Cricetulus
Humans
Ligands
Models, Molecular
Receptors, Neurotensin / agonists*
Chemical
Reg. No./Substance:
0/Ligands; 0/Receptors, Neurotensin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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