Biased signalling from the glucocorticoid receptor: Renewed opportunity for tailoring glucocorticoid activity

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• 作者：Christine R. Keenan ; Michael J. Lew ; Alastair G. Stewart ; ^{astew@unimelb.edu.au" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AP-1 ; activator protein 1 ; AR ; androgen receptor ; cAMP ; cyclic adenosine monophosphate ; p57 ; Kip2 ; cyclin-dependent kinase inhibitor 1C ; COX-2 ; cyclooxygenase-2 ; DC ; deisobutyrylciclesonide ; Dex ; dexamethasone ; KA ; dissociation constant ; ER ; oestrogen receptor ; ERK ; extracellular signal-regulated kinase ; FF ; fluticasone furoate ; GILZ ; glucocorticoid-induced leucine zipper ; GPCR ; G protein coupled receptor ; GR ; glucocorticoid receptor ; GRE ; glucocorticoid response element ; GRIP-1 ; glucocorticoid
• 刊名：Biochemical Pharmacology
• 出版年：2016
• 出版时间：15 July 2016
• 年：2016
• 卷：112
• 期：Complete
• 页码：6-12
• 全文大小：856 K

文摘

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.