An update of novel screening methods for GPCR in drug discovery.
BACKGROUND
G protein-coupled receptors (GPCRs) are the largest and most versatile group of cytomembrane receptors, comprising of approximately 300 non-sensory and druggable members. Traditional GPCR drug screening is based on radiometric competition binding assays, which are expensive and hazardous to human health. Furthermore, the paradox of high investment and low output, in terms of new drugs, highlights the need for more efficient and effective drug screening methods.


METHODS
This review summarizes non-radioactive assays assessing the ligand-receptor binding including: the fluorescence polarization assay, the TR-FRET assay and the surface plasmon resonance assay. It also looks at non-radioactive assays that assess receptor activation and signaling including: second messenger-based assays and β-arrestin recruitment-based assays. This review also looks at assays based on cellular phenotypic change.


CONCLUSIONS
GPCR signaling pathways look to be more complicated than previously thought. The existence of receptor allosteric sites and multireceptor downstream effectors restricts the traditional assay methods. The emergence of novel drug screening methods such as those for assessing β-arrestin recruitment and cellular phenotypic change may provide us with improved drug screening efficiency and effect.
Zhejiang University, Institute of Biochemistry and Molecular Biology, College of Life Sciences, Zijingang Campus, Yu-hang-tang Road No.866, Hangzhou, Zhejiang 310058, China.
Linjie
L
Chen
Lili
L
Jin
Naiming
N
Zhou
D000495:Allosteric Site; D001681:Biological Assay / Q000379:methods; D055808:Drug Discovery / Q000379:methods* / Q000592:standards; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
D043562:Receptors, G-Protein-Coupled