glucocorticoïdreceptorantagonist

Glucocorticoïdreceptorantagonist refers to compounds that bind to the glucocorticoid receptor (GR) and block the action of endogenous glucocorticoids such as cortisol. By occupying the receptor, these agents prevent glucocorticoid-driven changes in gene transcription and cellular responses, reducing the physiological effects of cortisol.

Most glucocorticoïdreceptorantagonists act as competitive antagonists, though some exhibit tissue-selective or context-dependent activity and may show partial agonism in certain settings. Many compounds under investigation are described as selective glucocorticoid receptor antagonists (SGRAs), aiming to limit adverse effects while preserving therapeutic benefit.

The most clinically established example is mifepristone (RU-486), which inhibits GR signaling and also antagonizes the progesterone receptor. It is approved for adult patients with hypercortisolism due to Cushing's syndrome, particularly when hyperglycemia or diabetes is present, and it is also used for other indications related to PR antagonism. Other glucocorticoïdreceptorantagonists, such as relacorilant and various research compounds (for example CORT-108297), are in development or exploratory use. These agents are being studied for conditions including Cushing's syndrome, metabolic disorders, mood and cognitive disorders, and certain cancers, where excessive glucocorticoid signaling may contribute to disease.

Safety and practical considerations include the risk of adrenal insufficiency if glucocorticoid signaling is suppressed too much, potential reproductive effects with compounds affecting the progesterone receptor, and drug interactions via pathways such as cytochrome P450 3A4. As a class, glucocorticoïdreceptorantagonists range from established therapies to investigational tools, with ongoing evaluation of their benefits and risks.