Inhibition and stimulation of activity of purified recombinant CYP11A1 by therapeutic agents

Mol Cell Endocrinol. 2013 May 22;371(1-2):100-6. doi: 10.1016/j.mce.2012.10.013. Epub 2012 Oct 23.


In vertebrates, the biosynthesis of steroid hormones is initiated by cytochrome P450 CYP11A1 which converts cholesterol to pregnenolone. We investigated whether some of the experimental and FDA-approved therapeutic agents alter the activity of CYP11A1 in the reconstituted system in vitro. We found that under the experimental conditions used and when phospholipids are included, ketoconazole, posaconazole, carbenoxolone, and selegiline inhibit CYP11A1-mediated production of pregnenolone by at least 67%. Conversely, pemirolast, clobenpropit, desogestrel, dexmedetomidine, and tizanidine stimulate the enzyme activity by up to 70%. We then evaluated the identified inhibitors and activators for spectral binding to CYP11A1 and their effect on enzyme activity in the absence of phospholipids. The data obtained provide insight into how different drugs interact with CYP11A1 and demonstrate that P450 association with the lipid bilayer determines, in many cases, a drug's effect on enzyme activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / biosynthesis
  • Cholesterol / metabolism
  • Cholesterol Side-Chain Cleavage Enzyme / antagonists & inhibitors*
  • Cholesterol Side-Chain Cleavage Enzyme / metabolism*
  • Enzyme Activators / metabolism
  • Enzyme Activators / pharmacology
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Phospholipids / metabolism
  • Pregnenolone / biosynthesis
  • Steroids / biosynthesis


  • Adrenal Cortex Hormones
  • Enzyme Activators
  • Enzyme Inhibitors
  • Phospholipids
  • Steroids
  • Pregnenolone
  • Cholesterol
  • Cholesterol Side-Chain Cleavage Enzyme