Publication
Title
Functional signaling biases in G protein-coupled receptors : game theory and receptor dynamics
Author
Abstract
Pharmacotherapeutic targeting of G protein-coupled receptors (GPCRs) is perhaps the most important field of drug design, as agents designed to control these receptors constitute more than half of the pharmacopeia. Initially GPCRs were considered to be unitary entities, possessing all of their potential functionality in their characteristic heptahelical core. Early models of the functional activity of GPCRs considered them to possess just a simple 'on' or 'off' status. Recent research however has allowed us to realize that GPCR functionality is dependent upon many other proteins outside of the heptahelical core, on the site of GPCR expression in a tissue or a microdomain in a cell, and, most importantly, on the formation of differential 'active' states preferentially coupled to specific signal transduction structures. The recognition of such signaling diversity has facilitated the ability to appreciate and identify ligands for GPCRs that demonstrate a bias towards one signaling form of a receptor to another. However while potentially increasing our ability for selective signal targeting, our approach to understanding the physiological ramifications of systemic signaling manipulation is underdeveloped. This explosion in the complexity of GPCR signaling is now becoming familiar territory to receptor biologists, yet the application of this knowledge to drug design is relatively limited. This review will attempt to outline potential pitfalls and unseen benefits of using signaling bias in therapeutic design as well as highlighting new applications such as Game Theory for uncovering new therapeutic applications for biased agonists.
Language
English
Source (journal)
Mini reviews in medicinal chemistry
Publication
2012
ISSN
1389-5575
DOI
10.2174/138955712800959071
Volume/pages
12 :9 (2012) , p. 831-840
ISI
000306521100005
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Project info
Publication type
Subject
External links
Web of Science
Record
Identifier
Creation 06.01.2015
Last edited 17.02.2023
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