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 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.

中文翻译：

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咪唑并[2,1- b ]苯并噻唑衍生物作为糖皮质激素受体的潜在变构抑制剂

糖皮质激素受体（GCR）反式激活报告基因试验被用作对1200种化合物的多元化文库的初步高通量筛选，以评估其作为GCR拮抗剂的作用。一类咪唑并[2,1- b ]苯并噻唑和咪唑并[2,1- b ]苯并咪唑衍生物利用GCR和NF-κB特异的报告基因检测方法，具有调节GCR反式激活和抗炎性抑制作用的能力。GCR配体结合域的晶体结构的模型研究提供了三个带有四氢咪唑[2,1- b]的新类似物能够在地塞米松（DEX）存在下拮抗GCR的]苯并噻唑支架，并且还定义了它们在GCR结构中的假定结合。在用新类似物处理的细胞上，GCR本身及其靶基因GILZ的mRNA水平测量均显示出GCR反式激活抑制作用，因此暗示了GCR的潜在变构抑制作用。