Publication
Title
Imidazo[2,1-b]benzothiazol derivatives as potential allosteric inhibitors of the glucocorticoid receptor
Author
Abstract
Glucocorticoid receptor (GCR) transactivation reporter gene assays were used as an initial high-throughput screening on a diversified library of 1200 compounds for their evaluation as GCR antagonists. A class of imidazo[2,1-b]benzothiazole and imidazo[2,1-b]benzoimidazole derivatives were identified for their ability to modulate GCR transactivation and antiinflammatory transrepression effects utilizing GCR and NF-kappa B specific reporter gene assays. Modeling studies on the crystallographic structure of the GCR ligand binding domain provided three new analogues bearing the tetrahydroimidazo[2,1-b]benzothiazole scaffold able to antagonize the GCR in the presence of dexamethasone (DEX) and also defined their putative binding into the GCR structure. Both mRNA level measures of GCR itself and its target gene GILZ, on cells treated with the new analogues, showed a GCR transactivation inhibition, thus suggesting a potential allosteric inhibition of the GCR.
Language
English
Source (journal)
ACS medicinal chemistry letters. - -
Publication
2018
ISSN
1948-5875
Volume/pages
9:4(2018), p. 339-344
ISI
000430256200008
Pubmed ID
29670697
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 12.06.2018
Last edited 02.09.2021
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