Science


The Role of GR-II Antagonists

Since its founding in 1998, Corcept has focused its research and clinical development activity on drugs that antagonize or block the glucocorticoid receptor or “GR-II” receptor, one of the body's two receptors for cortisol. Cortisol is a hormone essential for life, but is also implicated in a broad range of psychiatric and metabolic diseases when it loses its natural regulation. When cortisol is bound to the GR –II receptor, it triggers a cascade of signaling events leading — in healthy persons — to normal functioning. However, in others, abnormal levels of cortisol are translated by the signaling cascade to produce severe metabolic diseases and psychiatric disorders.

Molecular structure of Cortisol

Cortisol

Today, Corcept has in its research and development portfolio several GR-II antagonists. Extensive preclinical and clinical work is now in progress to evaluate the broad potential of this platform and its specific application for a number of metabolic and psychiatric disorders. The company has filed with the FDA a new drug application (or “NDA”) for one such drug, mifepristone, which is currently under FDA review.

The diseases in which cortisol may play a role (as cited in the published literature) and to which we may apply our technology include:

  • Cushing's Syndrome — Nieman (1985); van der Lely (1991); Fallo (2009); Leal-Cerro (2009); Whitworth (2005); Arnaldi (2003)
  • Psychotic Depression — Blasey, (2009); Wedeking (2007); Contreras (2007);
    Duval (2006); DeBattista (2006); Belanoff (2001); Blasey (2011)
  • Antipsychotic Induced Weight Gain — von Geldern (2004)
  • Diabetes — Rosmand (2003); Chiodini (2007)
  • Obesity — Frey et al, (2004); Vicennati (2009); Asagami (2011)
  • Hypertension — Kelly (1998); Inada (2008); Chamarthi (2007); Hammer (2006);
    Kaltsas (2002); Donovan (1999)
  • Osteoporosis — Sbaihi (2009); Chiodini (2007); Khanine (2000); Licata (1992)
  • Glaucoma — Carnahan (2000); Schwartz (1987)
  • Central Serious Retinopathy — Collucciello (2010); Neilsen (2007)
  • Alzheimer's Disease — Green (2006); Huang (2009)
  • Neurodegenerative Diseases — Sapolsky (2000)
  • Post-Traumatic Stress Disorder – Taubenfeld (2009); Pitman (2011)