title: Biased signalling from the glucocorticoid receptor: Renewed opportunity for tailoring glucocorticoid activity.
abstract: Recent landmark studies applying analytical pharmacology approaches to the glucocorticoid receptor (GR) have demonstrated that different ligands can cause differential activation of distinct GR-regulated genes. Drawing on concepts of signalling bias from the field of G protein-coupled receptor (GPCR) biology, we speculate that ligand-dependent differences in GR signalling can be considered analogous to GPCR biased signalling, and thus can be quantitatively analysed in a similar way. This type of approach opens up the possibility of using rational structure-based drug optimisation strategies to improve the therapeutic selectivity of glucocorticoid drugs to maximise their efficacy and minimise adverse effects.
authors.affiliation: Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Christine R
authors.initials: CR
authors.lastname: Keenan
authors.affiliation: Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lew
authors.affiliation: Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: astew@unimelb.edu.au.
authors.forename: Alastair G
authors.initials: AG
authors.lastname: Stewart
mesh_terms: D000818:Animals; D005938:Glucocorticoids / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D005938:Glucocorticoids; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011965:Receptors, Glucocorticoid
keywords: Corticosteroids; G protein-coupled receptors; Inflammation; Pharmacodynamics; Steroid resistance; Systems biology