Identification of dissociated non-steroidal glucocorticoid receptor agonists.

Article Details

Citation
Copy to clipboard

Kuzmich D, Kirrane T, Proudfoot J, Bekkali Y, Zindell R, Beck L, Nelson R, Shih CK, Kukulka AJ, Paw Z, Reilly P, Deleon R, Cardozo M, Nabozny G, Thomson D

Identification of dissociated non-steroidal glucocorticoid receptor agonists.

Bioorg Med Chem Lett. 2007 Sep 15;17(18):5025-31. Epub 2007 Jul 25.

PubMed ID
17692519 [ View in PubMed
]
Abstract

A new series of ligands for the glucocorticoid receptor (GR) is described. SAR development was guided by docking 3 into the GR active site and optimizing an unsubstituted phenyl ring for key interactions found in the steroid A-ring binding pocket. To identify compounds with an improved side effect profile over marketed steroids the functional activity of compounds was evaluated in cell based assays for transactivation (aromatase) and transrepression (IL-6). Through this effort, 36 has been identified as a partial agonist with a dissociated profile in these cell based assays.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
DexamethasoneGlucocorticoid receptorIC 50 (nM)3N/AN/ADetails