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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2007-12-18
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pubmed:abstractText |
A novel technology for monitoring the changes of 3,'5'-adenosine cyclic monophosphate (cAMP) in live cells suitable for drug screening relies on the use of cyclic nucleotide-gated channels as biosensors coexpressed with the appropriate target receptor. The technique (termed BD ACTOne) offers measurement of cAMP-dependent calcium influx or membrane depolarization with conventional fluorescent methods both in kinetic and in endpoint modes, optimal for high-throughput and subsequent compound screening. The utility of the technique is reported here based on assay development and high-throughput screening for small-molecule antagonists of the peptide parathyroid hormone 2 receptor (PTH2R). The dual-signaling properties of the receptor were retained in the recombinant system, and the observed pharmacological profile corresponded to data from radiolabeled cAMP determination. The membrane-potential-based high-throughput assay produced reproducible actives and led to the identification of several chemical scaffolds with potential utility as PTH2R ligands.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1087-0571
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1068-73
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pubmed:dateRevised |
2011-5-23
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pubmed:meshHeading |
pubmed-meshheading:18087071-Calcium,
pubmed-meshheading:18087071-Cell Line,
pubmed-meshheading:18087071-Cyclic AMP,
pubmed-meshheading:18087071-Cyclic Nucleotide-Gated Cation Channels,
pubmed-meshheading:18087071-Dose-Response Relationship, Drug,
pubmed-meshheading:18087071-Drug Evaluation, Preclinical,
pubmed-meshheading:18087071-Fluorescence,
pubmed-meshheading:18087071-GTP-Binding Protein alpha Subunits, Gs,
pubmed-meshheading:18087071-Humans,
pubmed-meshheading:18087071-Membrane Potentials,
pubmed-meshheading:18087071-Neuropeptides,
pubmed-meshheading:18087071-Receptor, Parathyroid Hormone, Type 1,
pubmed-meshheading:18087071-Receptors, G-Protein-Coupled,
pubmed-meshheading:18087071-Signal Transduction
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pubmed:year |
2007
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pubmed:articleTitle |
Application of the BD ACTOne technology for the high-throughput screening of Gs-coupled receptor antagonists.
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pubmed:affiliation |
Lead Discovery Unit, Gedeon Richter Plc, Budapest, Hungary. visegrady@richter.hu
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pubmed:publicationType |
Journal Article
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