Dissociated non-steroidal glucocorticoid receptor modulators:: an update on new compounds

被引：36

作者：

Schacke, Heike ^{[1
]}

Berger, Markus ^{[1
]}

Hansson, Thomas G. ^{[2
]}

McKerrecher, Darren ^{[2
]}

Rehwinkel, Hartmut ^{[1
]}

机构：

[1] Bayer Schering Pharma AG, Global Drug Discovery, D-13342 Berlin, Germany

[2] AstraZeneca Res & Dev, S-22223 Lund, Sweden

来源：

EXPERT OPINION ON THERAPEUTIC PATENTS | 2008年 / 18卷 / 03期

关键词：

glucocorticoids; glucocorticoid receptor; selective glucocorticoid receptor agonists;

D O I：

10.1517/13543776.18.3.339

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

Background: Glucocorticoids are the most potent anti-inflammatory drugs available and allow successful treatment of several chronic inflammatory and autoimmune diseases. The discovery of the molecular mechanisms of the glucocorticoid receptor (GR), and the recognition that activation and repression of gene expression could be addressed separately, opened the possibility of improving safety profiles by identifying ligands that predominantly induce repression over activation. Recent progress in the development of dissociated and other non-steroidal GR modulators is discussed here. Objective: To summarize the data and progress of current compounds reported in GR programs carried out by pharmaceutical companies. Methods: The review is primarily of patents and publications disclosed over the last two years. Results/conclusion: Although the mechanistic drivers for development of safer GR ligands have expanded from the basic transrepression/transactivation hypothesis, the concept appears to have led to the identification of some drug candidates that show dissociated in vitro profiles and improved in vivo therapeutic indices.

引用

页码：339 / 352

页数：14

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