Novel Glucocorticoid Receptor Ligands

Heike Schacke, Khusru Asadullah, Markus Berger, and Hartmut Rehwinkel 

Nuclear Receptors as Drug Targets. Edited by Eckhard Ottow and Hilmar Weinmann Copyright 2008 WILEY-VCH Veriag GmbH Co. KGaA, Weinheim ISBN 978-3-527-31872-8 

Although topical GCs usually have less side-effects than systemic GCs, and are successfully used to treat several inflammatory dermatological diseases, their major limitation remains the local side-effects they can cause. Furthermore, severe disease exacerbations often cannot be treated efficiently with compounds that work locally only. In such situations, systemic treatment is mandatory (e.g. in bullous skin diseases). In dermatological indications especially the main drawback of topical GCs is the development of skin atrophy after long-term use [11, 12], 

Therefore, there is a great medical need for GC-like compounds that possess both an antiinflammatory/immunomodulatory activity similar to the marketed GCs and a reduced risk of undesired effects. 

---

H. E. Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell 2002, no, 93-105. 

E. L., Willson, T.M., Lambert, M.H., Moore, J.T., Pearce, K.H. and Xu, H.E. (2002) Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell, 110, 93-105. 

F. Wust, K.E. Carlson, J.A. Katzenellenbogen, Synthesis of novel arylpyrazolo corticosteroids as potential ligands for imaging brain glucocorticoid receptors. Steroids 68 (2003) 177-191. 

---