4CSJ

The discovery of potent selective glucocorticoid receptor modulators, suitable for inhalation

Summary for 4CSJ

• Entry DOI: 10.2210/pdb4csj/pdb
• Descriptor: GLUCOCORTICOID RECEPTOR, NUCLEAR RECEPTOR COACTIVATOR 2, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: signaling protein, nuclear hormone receptor, ligand complex, peptide complex
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm. Isoform Beta: Nucleus: P04150
• Total number of polymer chains: 2
• Total formula weight: 34295.53

Authors

Edman, K.,Ahlgren, R.,Bengtsson, M.,Bladh, H.,Backstrom, S.,Dahmen, J.,Henriksson, K.,Hillertz, P.,Hulikal, V.,Jerre, A.,Kinchin, L.,Kase, C.,Lepisto, M.,Mile, I.,Nilsson, S.,Smailagic, A.,Taylor, J.,Tjornebo, A.,Wissler, L.,Hansson, T. (deposition date: 2014-03-07, release date: 2014-05-07, Last modification date: 2023-12-20)

Primary citation

Edman, K.,Ahlgren, R.,Bengtsson, M.,Bladh, H.,Backstrom, S.,Dahmen, J.,Henriksson, K.,Hillertz, P.,Hulikal, V.,Jerre, A.,Kinchin, L.,Kase, C.,Lepisto, M.,Mile, I.,Nilsson, S.,Smailagic, A.,Taylor, J.,Tjornebo, A.,Wissler, L.,Hansson, T.
The Discovery of Potent and Selective Non-Steroidal Glucocorticoid Receptor Modulators, Suitable for Inhalation.
Bioorg.Med.Chem.Lett., 24:2571-, 2014

PubMed Abstract: We report the discovery of highly potent and selective non-steroidal glucocorticoid receptor modulators with PK properties suitable for inhalation. A high throughput screen of the AstraZeneca compound collection identified sulfonamide 3 as a potent non-steroidal glucocorticoid receptor ligand. Further optimization of this lead generated indazoles 30 and 48 that were progressed to characterization in in vivo models. X-ray crystallography was used to gain further insight into the binding mode of selected ligands.

PubMed: 24755427
DOI: 10.1016/J.BMCL.2014.03.070

Experimental method

X-RAY DIFFRACTION (2.3 Å)