title: The potential of targeting CYP11B.
abstract: BACKGROUND
  Members of the CYP11B subfamily participate in the biosynthesis of important steroid hormones. CYP11B1 catalyzes the formation of cortisol, while CYP11B2 realizes the biosynthesis of aldosterone. Overproduction of cortisol is related to Cushing's disease, whereas overproduction of aldosterone leads to hypertension and end-organ damage such as cardiac and renal hypertrophy. Therefore, CYP11B1 and CYP11B2 have been defined as interesting targets for the development of novel drugs.
  
  
  METHODS
  The paper describes the CYP11B1 and CYP11B2 genes and proteins, giving special attention to their functional and structural properties, the development of efficient test systems for potential inhibitors of both CYPs and the development and testing of novel potential drugs on the basis of selective inhibition of CYP11B1 and CYP11B2.
  
  
  CONCLUSIONS
  The availability of relevant and efficient screening systems for testing the effects of inhibitors of human CYP11B1 and CYP11B2, combined with experiences and success in synthesizing selective and efficient inhibitors of these isoenzymes, provides a realistic basis for a successful development of drugs using CYP11B1 and CYP11B2 as targets. The first clinical trials with the CYP11B2 inhibitor LCI699 demonstrated some side effects but showed inhibition of end-organ damage in animals, indicating that it might be a useful lead compound for future developments.
authors: a Lehrstuhl für Biochemie , Universität des Saarlandes , Saarbrücken , Germany.
authors: Rita
authors: R
authors: Bernhardt
mesh_terms: D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy / Q000473:pathology; D019405:Cytochrome P-450 CYP11B2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology; D007527:Isoenzymes; D007674:Kidney Diseases / Q000188:drug therapy / Q000473:pathology; D058990:Molecular Targeted Therapy; D011725:Pyridines / Q000494:pharmacology; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D007093:Imidazoles; D007527:Isoenzymes; D011725:Pyridines; D000450:Aldosterone; C553306:Osilodrostat; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase
keywords: Adrenodoxin; CYP11B1; CYP11B2; Cushing’s disease; LCI699; NADPH-cytochrome P450 reductase; adrenodoxin reductase; aldosterone; aldosteronism; corticosterone; cortisol; cytochrome P450