Dataset Information

Imidazo[2,1-b]benzothiazol Derivatives as Potential Allosteric Inhibitors of the Glucocorticoid Receptor.

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 anti-inflammatory transrepression effects utilizing GCR and NF-?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.

SUBMITTER: Christodoulou MS

PROVIDER: S-EPMC5900336 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Imidazo[2,1-b]benzothiazol Derivatives as Potential Allosteric Inhibitors of the Glucocorticoid Receptor.

Christodoulou Michael S MS Dapiaggi Federico F Ghiringhelli Francesca F Pieraccini Stefano S Sironi Maurizio M Lucafò Marianna M Curci Debora D Decorti Giuliana G Stocco Gabriele G Chirumamilla Chandra Sekhar CS Vanden Berghe Wim W Balaguer Patrick P Michel Benoît Y BY Burger Alain A Beccalli Egle M EM Passarella Daniele D Martinet Nadine N

ACS medicinal chemistry letters 20180226 4

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 anti-inflammatory transrepression effects utilizing GCR and NF-κB specific reporter gene assays. Modeling studies on the crystallog ...[more]

PMID: 29670697

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Dataset Information

Imidazo[2,1-b]benzothiazol Derivatives as Potential Allosteric Inhibitors of the Glucocorticoid Receptor.

Publications

Imidazo[2,1-<i>b</i>]benzothiazol Derivatives as Potential Allosteric Inhibitors of the Glucocorticoid Receptor.

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