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Novel Selective CYP11B1 Inhibitors - Cushing's, metabolic syndrome treatment

Organization name

PVA Saarland



Steroid-11β-hydroxylase (CYP11B1) is localised in the adrenal cortex and plays a crucial role in glucocorticoid formation. Elevated cortisol levels are associated with Cushing’s syndrome or metabolic disease. As CYP11B1 catalyses the final step in cortisol biosynthesis, its inhibition with selective compounds is a promising strategy for the treatment of these diseases. There are inhibitors of cortisol biosynthesis such as Ketoconazole, Etomidate or Metyrapone in clinical use, but all of them show severe side effects due to the fact that they are unselective against other steroidogenic CYP enzymes (CYP11B2, CYP17, CYP19). A special challenge in the development of CYP11B1 inhibitors is to reach sufficient selectivity versus CYP11B2, the key enzyme in mineralocorticoid biosynthesis, as both enzymes show an enormously high identity of 93 %.


Scientists of Saarland University have recently succeeded in developing the first CYP11B1 inhibitors showing good selectivity. As starting point the highly active CYP11B1 inhibitor Etomidate has been used. Via several modifications followed by further optimizations realized at this molecule, it was possible to increase the selectivity resulting in a very weak inhibition towards CYP11B2 and no inhibition of CYP17 and CYP19. Activities of the inhibitors are also comparable to Ketoconazole and Metyrapone that are already used in clinical practice. The newly synthesized CYP11B1 inhibitors show superior selectivities to the known active agents in an outstanding manner.

For data please see the flyer.


  • Selective effect on CYP11B1-enzymes
  • very small weak to non- inhibition towards other steroidogenic CYP-enzymes
  • Outstanding activities
  • Treatment of Cushing's syndrome
  • Treatment of metabolic syndrome

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