Synthesis of novel steroidal agonists, partial agonists, and antagonists for the glucocorticoid receptor.
Bioorg Med Chem Lett
; 27(2): 347-353, 2017 01 15.
Article
em En
| MEDLINE
| ID: mdl-27919657
ABSTRACT
Adverse effects of glucocorticoids could be limited by developing new compounds that selectively modulate anti-inflammatory activity of the glucocorticoid receptor (GR). We have synthesized a novel series of steroidal GR ligands, including potent agonists, partial agonists and antagonists with a wide range of effects on inhibiting secretion of interleukin-6. Some of these new ligands were designed to directly impact conformational stability of helix-12, in the GR ligand-binding domain (LBD). These compounds modulated GR activity and glucocorticoid-induced gene expression in a manner that was inversely correlated to the degree of inflammatory response. In contrast, compounds designed to directly modulate LBD epitopes outside helix-12, led to dissociated levels of GR-mediated gene expression and inflammatory response. Therefore, these new series of compounds and their derivatives will be useful to dissect the ligand-dependent features of GR signaling specificity.
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Base de dados:
MEDLINE
Assunto principal:
Esteroides
/
Receptores de Glucocorticoides
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article