High-Throughput Screening Campaign Identified a Potential Small Molecule RXFP3/4 Agonist

Guangyao Lin; Yang Feng; Xiaoqing Cai; Caihong Zhou; Lijun Shao; Yan Chen; Linhai Chen; Qing Liu; Qingtong Zhou; Ross A.D. Bathgate; Dehua Yang; Ming-Wei Wang

doi:10.3390/molecules26247511

Molecules (Dec 2021)

High-Throughput Screening Campaign Identified a Potential Small Molecule RXFP3/4 Agonist

Guangyao Lin,
Yang Feng,
Xiaoqing Cai,
Caihong Zhou,
Lijun Shao,
Yan Chen,
Linhai Chen,
Qing Liu,
Qingtong Zhou,
Ross A.D. Bathgate,
Dehua Yang,
Ming-Wei Wang

Affiliations

Guangyao Lin: The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Yang Feng: The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Xiaoqing Cai: The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Caihong Zhou: The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Lijun Shao: University of Chinese Academy of Sciences, Beijing 100049, China
Yan Chen: Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Linhai Chen: The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Qing Liu: The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Qingtong Zhou: Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Ross A.D. Bathgate: Florey Institute of Neuroscience and Mental Health and Department of Biochemistry and Pharmacology, The University of Melbourne, Parkville, VIC 3052, Australia
Dehua Yang: The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Ming-Wei Wang: The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

DOI: https://doi.org/10.3390/molecules26247511
Journal volume & issue: Vol. 26, no. 24
p. 7511

Abstract

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Relaxin/insulin-like family peptide receptor 3 (RXFP3) belongs to class A G protein-coupled receptor family. RXFP3 and its endogenous ligand relaxin-3 are mainly expressed in the brain with important roles in the regulation of appetite, energy metabolism, endocrine homeostasis and emotional processing. It is therefore implicated as a potential target for treatment of various central nervous system diseases. Since selective agonists of RXFP3 are restricted to relaxin-3 and its analogs, we conducted a high-throughput screening campaign against 32,021 synthetic and natural product-derived compounds using a cyclic adenosine monophosphate (cAMP) measurement-based method. Only one compound, WNN0109-C011, was identified following primary screening, secondary screening and dose-response studies. Although displayed agonistic effect in cells overexpressing the human RXFP3, it also showed cross-reactivity with the human RXFP4. This hit compound may provide not only a chemical probe to investigate the function of RXFP3/4, but also a novel scaffold for the development of RXFP3/4 agonists.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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