Document Detail

Identification of Small-Molecule Agonists of Human Relaxin Family Receptor 1 (RXFP1) by Using a Homogenous Cell-Based cAMP Assay.
MedLine Citation:
PMID:  23212924     Owner:  NLM     Status:  Publisher    
The relaxin hormone is involved in a variety of biological functions, including female reproduction and parturition, as well as regulation of cardiovascular, renal, pulmonary, and hepatic functions. It regulates extracellular matrix remodeling, cell invasiveness, proliferation, differentiation, and overall tissue homeostasis. The G protein-coupled receptor (GPCR) relaxin family receptor 1 (RXFP1) is a cognate relaxin receptor that mainly signals through cyclic AMP second messenger. Although agonists of the receptor could have a wide range of pharmacologic utility, until now there have been no reported small-molecule agonists for relaxin receptors. Here, we report the development of a quantitative high-throughput platform for an RXFP1 agonist screen based on homogenous cell-based HTRF cyclic AMP (cAMP) assay technology. Two small molecules of similar structure were independently identified from a screen of more than 365 677 compounds. Neither compound showed activity in a counterscreen with HEK293T cells transfected with an unrelated GPCR vasopressin 1b receptor. These small-molecule agonists also demonstrated selectivity against the RXFP2 receptor, providing a basis for future medicinal chemistry optimization of selective relaxin receptor agonists.
Catherine Z Chen; Noel Southall; Jingbo Xiao; Juan J Marugan; Marc Ferrer; Xin Hu; Raisa E Jones; Shu Feng; Irina U Agoulnik; Wei Zheng; Alexander I Agoulnik
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-4
Journal Detail:
Title:  Journal of biomolecular screening     Volume:  -     ISSN:  1552-454X     ISO Abbreviation:  J Biomol Screen     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9612112     Medline TA:  J Biomol Screen     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
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