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Discovery & Development

Focusing on the Adverse Effects of Excess Cortisol

The adverse effects of excess cortisol have been Corcept’s focus since the company’s inception. Abnormal levels and release of cortisol play a role in a variety of metabolic, oncological, and psychiatric diseases, and we are currently studying a new generation of compounds that may mitigate the effects of excess cortisol.

In addition to our work with mifepristone, we have developed over 300 proprietary molecules, advancing the most promising of these to the clinic to see if they can mitigate the effects of excess cortisol and the serious, sometimes life-threatening conditions that may result. All of these compounds competitively block the glucocorticoid receptor (GR), but not the progesterone receptor.

Scientific literature suggests that competitive GR antagonism may have a role in treating many conditions, including post-traumatic stress disorder, mild cognitive impairment, Alzheimer’s disease, alcoholism, prostate, breast and ovarian cancer, and weight gain caused by atypical anti-psychotic medications. We are investigating several of these indications in collaboration with researchers around the world.

Mechanism of Action

Cortisol acts by binding to the glucocorticoid receptor (GR). GR antagonists block the effects of excess cortisol by competing with cortisol’s ability to bind to GR. This does not decrease cortisol production but reduces the clinical impact of excess cortisol (hypercortisolism).

While mifepristone blocks both the glucocorticoid and progesterone receptors, Corcept is studying a new generation of compounds that block only GR. In both cases, there is little if any negative effect on mineralocorticoid (MR) activity.

Hypercortisolism has an impact on a wide range of conditions, including Cushing’s syndrome, anti-psychotic drug induced weight gain, diabetes, obesity, hypertension, Alzheimer’s disease, post-traumatic stress disorder, alcoholism, prostate, breast and ovarian cancer.

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