skip to main content
Language:
Search Limited to: Search Limited to: Resource type Show Results with: Show Results with: Search type Index

Biased agonism: An emerging paradigm in GPCR drug discovery

Bioorganic & medicinal chemistry letters, 2016-01, Vol.26 (2), p.241 [Peer Reviewed Journal]

Copyright © 2015 Elsevier Ltd. All rights reserved. ;EISSN: 1464-3405 ;DOI: 10.1016/j.bmcl.2015.12.024 ;PMID: 26707396

Digital Resources/Online E-Resources

Citations Cited by
  • Title:
    Biased agonism: An emerging paradigm in GPCR drug discovery
  • Author: Rankovic, Zoran ; Brust, Tarsis F ; Bohn, Laura M
  • Subjects: Animals ; Arrestins - agonists ; Arrestins - physiology ; Drug Discovery ; Humans ; Ligands ; Models, Molecular ; Receptors, G-Protein-Coupled - agonists ; Receptors, G-Protein-Coupled - physiology
  • Is Part Of: Bioorganic & medicinal chemistry letters, 2016-01, Vol.26 (2), p.241
  • Description: G protein coupled receptors have historically been one of the most druggable classes of cellular proteins. The members of this large receptor gene family couple to primary effectors, G proteins, that have built in mechanisms for regeneration and amplification of signaling with each engagement of receptor and ligand, a kinetic event in itself. In recent years GPCRs, have been found to interact with arrestin proteins to initiate signal propagation in the absence of G protein interactions. This pinnacle observation has changed a previously held notion of the linear spectrum of GPCR efficacy and uncovered a new paradigm in GPCR research and drug discovery that relies on multidimensionality of GPCR signaling. Ligands were found that selectively confer activity in one pathway over another, and this phenomenon has been referred to as 'biased agonism' or 'functional selectivity'. While great strides in the understanding of this phenomenon have been made in recent years, two critical questions still dominate the field: How can we rationally design biased GPCR ligands, and ultimately, which physiological responses are due to G protein versus arrestin interactions? This review will discuss the current understanding of some of the key aspects of biased signaling that are related to these questions, including mechanistic insights in the nature of biased signaling and methods for measuring ligand bias, as well as relevant examples of drug discovery applications and medicinal chemistry strategies that highlight the challenges and opportunities in this rapidly evolving field.
  • Publisher: England
  • Language: English
  • Identifier: EISSN: 1464-3405
    DOI: 10.1016/j.bmcl.2015.12.024
    PMID: 26707396
  • Source: MEDLINE
Back to results list
INSPIRE LIBRARY - TON DUC THANG UNIVERSITY (84-028) 37 755 057 Feedback
19 Nguyen Huu Tho St. Dist.7, HCM thuvien@tdtu.edu.vn

Copyright © 2017 INSPIRE LIBRARY - TON DUC THANG UNIVERSITY

Searching Remote Databases, Please Wait