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ACS Chem Neurosci. 2010 Aug 18;1(8):559-574.

Selective Modulation of Gq/Gs pathways by Naphtho Pyrano Pyrimidines as antagonists of the Neuropeptide S Receptor.

McCoy JG, Marugan JJ, Liu K, Zheng W, Southall N, Huang W, Heilig M, Austin CP.

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NIH Chemical Genomic Center, National Human Genome Research Institute, National Institutes of Heath, 9800 Medical Center Drive, Rockville, 20850, MD, USA.

Abstract

Antagonists of the Neuropeptide S Receptor have been postulated as promising therapeutics in the treatment of respiratory, sleep, anxiety, and addictive disorders. Here we present the SAR of a new series of orthosteric antagonists. Neuropeptide S Receptor signaling is coupled to both Gq and Gs proteins, and we observe that different analogues in this structural series can selectively antagonize these two pathways. Many G-protein coupled receptors transduce signals through multiple pathways. Selective antagonism of these pathways may lead the way to the development of more targeted pharmacological profiles and therapies.

PMID:: 21116448; [PubMed]
PMCID:: PMC2992437

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ZIA HG200319-06/HG/NHGRI NIH HHS/United States

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