Recent advances in the development of novel glucocorticoid receptor modulators

被引：36

作者：

Berlin, Michael ^{[1
]}

机构：

[1] Merck Res Labs, Dept Chem Res, Kenilworth, NJ 07033 USA

来源：

EXPERT OPINION ON THERAPEUTIC PATENTS | 2010年 / 20卷 / 07期

关键词：

anti-inflammatory; glucocorticoid receptor; modulation of gene expression; nonsteroidal glucocorticoids; transactivation; transrepression; PROTEASE-ACTIVATED RECEPTORS; MYOCARDIAL ISCHEMIA/REPERFUSION INJURY; CELL-PROLIFERATION; PLATELET ACTIVATION; PAR-1; ANTAGONISTS; PEPTIDE MIMETICS; THROMBIN; INHIBITION; DISCOVERY; POTENT;

D O I：

10.1517/13543776.2010.493876

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Importance of the field: The glucocorticoid receptor plays a number of fundamental roles in human physiology. Glucocorticosteroids are the ultimate anti-inflammatory and immunosuppressive agents highly efficacious in the treatment of serious diseases, but also associated with serious side effects. Improvement in the therapeutic profiles of drugs, acting at the glucocorticoid receptor, is highly desired and may potentially arise from the separation of their gene transactivating and gene transrepressing properties. Areas covered in this review: The review summarizes progress towards novel glucocorticoid drug candidates as indicated by the patent applications over the last 2 years (2008 - 2009). A brief discussion of glucocorticoid receptor biology and previous drug candidates is included. What the reader will gain: The understanding of the structural scope and biological profiles of the glucocorticoid receptor modulators, currently in preclinical and clinical development, based on the review of over 80 composition-of-matter and method-of-use patent applications. Take home message: The information on the good chemotypical diversity of glucocorticoid receptor modulators needs to be supplemented by the clinical data - presumably, soon to become available - to allow a look into a possible improvement in therapeutic index over the classic glucocorticosteroids.

引用

页码：855 / 873

页数：19

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