The potential of targeting CYP11B

References

• Bernhardt R, Waterman MR. Cytochrome P450 and steroid hormone biosynthesis. In: Sigel A, Sigel H, Sigel RKO, editors. The ubiquitous roles of cytochrome P450 proteins. 3. Chichester, UK: John Wiley & Sons; 2007. p. 361–369.
   Google Scholar
• Schiffer L, Anderko S, Hannemann F, et al. The CYP11B subfamily. J Steroid Biochem Mol Biol. 2015;151:38–51.
   PubMed Web of Science ®Google Scholar
• Kawamoto T, Mitsuuchi Y, Ohnishi T, et al. Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism. Biochem Biophys Res Commun. 1990;173:309–316.
   PubMed Web of Science ®Google Scholar
• Kawamoto T, Mitsuuchi Y, Toda K, et al. Cloning of cDNA and genomic DNA for human cytochrome P-45011 beta. FEBS Lett. 1990;269:345–349.
   PubMed Web of Science ®Google Scholar
• Mornet E, Dupont J, Vitek A, et al. Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta). J Biol Chem. 1989;264:20961–22067.
   PubMed Web of Science ®Google Scholar
• Erdmann B, Denner K, Gerst H, et al. Human adrenal CYP11B1: localization by in situ-hybridization and functional expression in cell cultures. Endocr Res. 1995;21:425–435.
   PubMed Web of Science ®Google Scholar
• Erdmann B, Gerst H, Bulow H, et al. Zone-specific localization of cytochrome P45011B1 in human adrenal tissue by PCR-derived riboprobes. Histochem Cell Biol. 1995;104:301–307.
   PubMed Web of Science ®Google Scholar
• Pascoe L, Jeunemaitre X, Lebrethon MC, et al. Glucocorticoid-suppressible hyperaldosteronism and adrenal tumors occurring in a single French pedigree. J Clin Invest. 1995;96:2236–2246.
   PubMed Web of Science ®Google Scholar
• Bernhardt R. Cytochrome P450: structure, function, and generation of reactive oxygen species. Rev Physiol Biochem Pharmacol. 1996;127:137–221.
   PubMed Web of Science ®Google Scholar
• Hannemann F, Bichet A, Ewen KM, et al. Cytochrome P450 systems–biological variations of electron transport chains. Biochim Biophys Acta. 2007;1770:330–344.
   PubMed Web of Science ®Google Scholar
• MacKenzie SM, Connell JM, Davies E, Non-adrenal synthesis of aldosterone: a reality check. Mol Cell Endocrinol. 2012;350:163–167.
   PubMed Web of Science ®Google Scholar
• White PC, Slutsker L. Haplotype analysis of CYP11B2. Endocr Res. 1995;21:437–442.
   PubMed Web of Science ®Google Scholar
• Ogishima T, Shibata H, Shimada H, et al. Aldosterone synthase cytochrome P-450 expressed in the adrenals of patients with primary aldosteronism. J Biol Chem. 1991;266:10731–10734.
   PubMed Web of Science ®Google Scholar
• Bureik M, Lisurek M, Bernhardt R. The human steroid hydroxylases CYP1B1 and CYP11B2. Biol Chem. 2002;383:1537–1551.
   PubMed Web of Science ®Google Scholar
• Curnow KM, Tusie-Luna MT, Pascoe L, et al. The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex. Mol Endocrinol. 1991;5:1513–1522.
   PubMed Web of Science ®Google Scholar
• Denner K, Doehmer J, Bernhardt R. Cloning of CYP11B1 and CYP11B2 from normal human adrenal and their functional expression in COS-7 and V79 Chinese hamster cells. Endocr Res. 1995;21:443–448.
   PubMed Web of Science ®Google Scholar
• Lisurek M, Bernhardt R. Modulation of aldosterone and cortisol synthesis on the molecular level. Mol Cell Endocrinol. 2004;215:149–159.
   PubMed Web of Science ®Google Scholar
• Mulatero P, Curnow KM, Aupetit-Faisant B, et al. Recombinant CYP11B genes encode enzymes that can catalyze conversion of 11-deoxycortisol to cortisol, 18-hydroxycortisol, and 18-oxocortisol. J Clin Endocrinol Metab. 1998;83:3996–4001.
   PubMed Web of Science ®Google Scholar
• Strushkevich N, Gilep AA, Shen L, et al. Structural insights into aldosterone synthase substrate specificity and targeted inhibition. Mol Endocrinol. 2013;27:315–324.
   PubMed Web of Science ®Google Scholar
• Zollner A, Kagawa N, Waterman MR, et al. Purification and functional characterization of human 11beta hydroxylase expressed in Escherichia coli. FEBS J. 2008;275:799–810. Epub 2008/01/25.
   PubMed Web of Science ®Google Scholar
• Kawamoto T, Mitsuuchi Y, Toda K, et al.. Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans. Proc Natl Acad Sci USA. 1992;89:1458–1462.
   PubMed Web of Science ®Google Scholar
• Hobler A, Kagawa N, Hutter MC, et al. Human aldosterone synthase: recombinant expression in E. coli and purification enables a detailed biochemical analysis of the protein on the molecular level. J Steroid Biochem Mol Biol. 2012;132:57–65.
   PubMed Web of Science ®Google Scholar
• Schloms L, Storbeck KH, Swart P, et al. The influence of Aspalathus linearis (Rooibos) and dihydrochalcones on adrenal steroidogenesis: quantification of steroid intermediates and end products in H295R cells. J Steroid Biochem Mol Biol. 2012;128:128–138.
   PubMed Web of Science ®Google Scholar
• Swart AC, Storbeck K-H. 11β-hydroxyandrostenedione: downstream metabolism by 11βHSD, 17βHSD and SRD5A produces novel substrates in familiar pathways. Mol Cell Endocrinol. 2015;408:114–123.
   PubMed Web of Science ®Google Scholar
• Parr MK, Zollner A, Fussholler G, et al. Unexpected contribution of cytochrome P450 enzymes CYP11B2 and CYP21, as well as CYP3A4 in xenobiotic androgen elimination - insights from metandienone metabolism. Toxicol Lett. 2012;213:381–391.
   PubMed Web of Science ®Google Scholar
• Zollner A, Parr MK, Dragan CA, et al. CYP21-catalyzed production of the long-term urinary metandienone metabolite 17beta-hydroxymethyl-17 alpha-methyl-18-norandrosta-1,4,13-trien-3-one: a contribution to the fight against doping. Biol Chem. 2010;391:119–127.
   PubMed Web of Science ®Google Scholar
• Schiffer L, Brixius-Anderko S, Hannemann F, et al. Metabolism of oral-turinabol by human steroid hormone-synthesizing cytochromes P450. Drug Metab Dispos. 2015;44:227–237.
   PubMed Web of Science ®Google Scholar
• Lund BO, Lund J. Novel involvement of a mitochondrial steroid hydroxylase (P450c11) in xenobiotic metabolism. J Biol Chem. 1995;270:20895–20897.
   PubMed Web of Science ®Google Scholar
• Schuster I, Bernhardt R, Inhibition of cytochromes p450: existing and new promising therapeutic targets. Drug Metab Rev. 2007;39:481–499.
   PubMed Web of Science ®Google Scholar
• Overington JP, Al-Lazikani B, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov. 2006;5:993–996.
   PubMed Web of Science ®Google Scholar
• Chua SC, Szabo P, Vitek A, et al. Cloning of cDNA encoding steroid 11 beta-hydroxylase (P450c11). Proc Natl Acad Sci U S A. 1987;84:7193–7197.
   PubMed Web of Science ®Google Scholar
• Wagner MJ, Ge Y, Siciliano M, et al. A hybrid cell mapping panel for regional localization of probes to human chromosome 8. Genomics. 1991;10:114–125.
   PubMed Web of Science ®Google Scholar
• Hampf M, Dao NT, Hoan NT, et al. Unequal crossing-over between aldosterone synthase and 11beta-hydroxylase genes causes congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2001;86:4445–4452.
   PubMed Web of Science ®Google Scholar
• Lifton RP, Dluhy RG, Powers M, et al. A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature. 1992;355:262–265.
   PubMed Web of Science ®Google Scholar
• MacConnachie AA, Kelly KF, McNamara A, et al. Rapid diagnosis and identification of cross-over sites in patients with glucocorticoid remediable aldosteronism. J Clin Endocrinol Metab. 1998;83:4328–4331.
   PubMed Web of Science ®Google Scholar
• Pascoe L, Curnow KM, Slutsker L, et al. Glucocorticoid-suppressible hyperaldosteronism results from hybrid genes created by unequal crossovers between CYP11B1 and CYP11B2. Proc Natl Acad Sci U S A. 1992;89:8327–8331.
   PubMed Web of Science ®Google Scholar
• Peters J, Hampf M, Peters B, et al.. Handbuch der Molekularen Medizin. In: Ganten D, Ruckpaul K, editors. Molekularbiologie,Klinik und Therapie steroidbedingter Hypertonien. Berlin: Springer Verlag; 1998. p. 413–452.
   Google Scholar
• Peter M. Congenital adrenal hyperplasia: 11beta-hydroxylase deficiency. Semin Reprod Med. 2002;20:249–254.
   PubMed Web of Science ®Google Scholar
• White PC. Aldosterone synthase deficiency and related disorders. Mol Cell Endocrinol. 2004;217:81–87.
   PubMed Web of Science ®Google Scholar
• Ferrari P. Genetics of the mineralocorticoid system in primary hypertension. Curr Hypertens Rep. 2002;4:18–24.
   PubMed Web of Science ®Google Scholar
• Lifton RP, Gharavi AG, Geller DS. Molecular mechanisms of human hypertension. Cell. 2001;104:545–556.
   PubMed Web of Science ®Google Scholar
• White PC. Steroid 11 beta-hydroxylase deficiency and related disorders. Endocrinol Metab Clin North Am. 2001;30:61–79.
   PubMed Web of Science ®Google Scholar
• Pitt B, Williams G, Remme W, et al. The EPHESUS trial: eplerenone in patients with heart failure due to systolic dysfunction complicating acute myocardial infarction. Eplerenone Post-AMI Heart Failure Efficacy and Survival Study. Cardiovasc Drugs Ther. 2001;15:79–87.
   PubMed Web of Science ®Google Scholar
• Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341:709–717.
   PubMed Web of Science ®Google Scholar
• Williams TA, Mulatero P, Bidlingmaier M, et al. Genetic and potential autoimmune triggers of primary aldosteronism. Hypertension. 2015;66:248–253.
   PubMed Web of Science ®Google Scholar
• Rossi GP, Bernini G, Caliumi C, et al. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol. 2006;48:2293–2300.
   PubMed Web of Science ®Google Scholar
• Calhoun DA, Nishizaka MK, Zaman MA, et al. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension. 2002;40:892–896.
   PubMed Web of Science ®Google Scholar
• Gomez-Sanchez CE, Oki K. Minireview: potassium channels and aldosterone dysregulation: is primary aldosteronism a potassium channelopathy? Endocrinology. 2014;155:47–55.
   PubMed Web of Science ®Google Scholar
• Lenzini L, Rossitto G, Maiolino G, et al. A meta-analysis of somatic KCNJ5 K+ channel mutations in 1636 patients with an aldosterone-producing adenoma. J Clin Endocrinol Metabolism. 2015;100:E1089–E95.
   PubMed Web of Science ®Google Scholar
• Fernandes-Rosa FL, Williams TA, Riester A, et al. Genetic spectrum and clinical correlates of somatic mutations in aldosterone-producing adenoma. Hypertension. 2014;64:354–361.
   PubMed Web of Science ®Google Scholar
• Hakki T, Bernhardt R. CYP17- and CYP11B-dependent steroid hydroxylases as drug development targets. Pharmacol Ther. 2006;111:27–52.
   PubMed Web of Science ®Google Scholar
• Hargovan M, Ferro A. Aldosterone synthase inhibitors in hypertension: current status and future possibilities. JRSM Cardiovasc Dis. 2014;3:1–9
   Google Scholar
• Namsolleck P, Unger T. Aldosterone synthase inhibitors in cardiovascular and renal diseases. Nephrol Dial Transplant. 2014;29:i62–i8.
   Google Scholar
• Denner K, Vogel R, Schmalix W, et al. Cloning and stable expression of the human mitochondrial cytochrome P45011B1 cDNA in V79 Chinese hamster cells and their application for testing of potential inhibitors. Pharmacogenetics. 1995;5:89–96.
   PubMedGoogle Scholar
• Denner K, Bernhardt R. Inhibition studies of steroid conversions mediated by human CYP11B1and CYP11B2 expressed in cell cultures. In: Ishimura Y, Shimada H, Suematsu M, editors. Oxygen homeostasis and its dynamics. Berlin: Springer-Verlag; 1998. p. 231–236.
   Google Scholar
• Ehmer PB, Bureik M, Bernhardt R, et al. Development of a test system for inhibitors of human aldosterone synthase (CYP11B2): screening in fission yeast and evaluation of selectivity in V79 cells. J Steroid Biochem Mol Biol. 2002;81:173–179.
   PubMed Web of Science ®Google Scholar
• Ulmschneider S, Muller-Vieira U, Klein CD, et al. Synthesis and evaluation of (pyridylmethylene)tetrahydronaphthalenes/-indanes and structurally modified derivatives: potent and selective inhibitors of aldosterone synthase. J Med Chem. 2005;48:1563–1575.
   PubMed Web of Science ®Google Scholar
• Ulmschneider S, Muller-Vieira U, Mitrenga M, et al. Synthesis and evaluation of imidazolylmethylenetetrahydronaphthalenes and imidazolylmethyleneindanes: potent inhibitors of aldosterone synthase. J Med Chem. 2005;48:1796–1805.
   PubMed Web of Science ®Google Scholar
• Bureik M, Hubel K, Dragan CA, et al. Development of test systems for the discovery of selective human aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) inhibitors. Discovery of a new lead compound for the therapy of congestive heart failure, myocardial fibrosis and hypertension. Mol Cell Endocrinol. 2004;217:249–254.
   PubMed Web of Science ®Google Scholar
• Voets M, Antes I, Scherer C, et al. Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial fibrosis. J Med Chem. 2006;49:2222–2231.
   PubMed Web of Science ®Google Scholar
• Roumen L, Sanders MP, Pieterse K, et al. Construction of 3D models of the CYP11B family as a tool to predict ligand binding characteristics. J Comput Aided Mol Des. 2007;21:455–471.
   PubMed Web of Science ®Google Scholar
• Roumen L, Peeters JW, Emmen JM, et al. Synthesis, biological evaluation, and molecular modeling of 1-benzyl-1H-imidazoles as selective inhibitors of aldosterone synthase (CYP11B2). J Med Chem. 2010;53:1712–1725.
   PubMed Web of Science ®Google Scholar
• Hoyt SB, Park MK, London C, et al. Discovery of Benzimidazole CYP11B2 Inhibitors with in Vivo Activity in Rhesus Monkeys. ACS Med Chem Lett. 2015;6:573–578.
   PubMed Web of Science ®Google Scholar
• Hu Q, Yin L, Ali A, et al. Novel pyridyl substituted 4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines as potent and selective aldosterone synthase inhibitors with improved in vitro metabolic stability. J Med Chem. 2015;58:2530–2537.
   PubMed Web of Science ®Google Scholar
• Freel EM, Shakerdi LA, Friel EC, et al. Studies on the origin of circulating 18-hydroxycortisol and 18-oxocortisol in normal human subjects. J Clin Endocrinol Metab. 2004;89:4628–4633.
   PubMed Web of Science ®Google Scholar
• LaSala D, Shibanaka Y, Jeng AY. Coexpression of CYP11B2 or CYP11B1 with adrenodoxin and adrenodoxin reductase for assessing the potency and selectivity of aldosterone synthase inhibitors. Anal Biochem. 2009;394:56–61.
   PubMed Web of Science ®Google Scholar
• Muller-Vieira U, Angotti M, Hartmann RW. The adrenocortical tumor cell line NCI-H295R as an in vitro screening system for the evaluation of CYP11B2 (aldosterone synthase) and CYP11B1 (steroid-11beta-hydroxylase) inhibitors. J Steroid Biochem Mol Biol. 2005;96:259–270.
   PubMed Web of Science ®Google Scholar
• Cerny MA, Csengery A, Schmenk J, et al. Development of CYP11B1 and CYP11B2 assays utilizing homogenates of adrenal glands: utility of monkey as a surrogate for human. J Steroid Biochem Mol Biol. 2015;154:197–205.
   PubMed Web of Science ®Google Scholar
• Yurek D, Yu L, Schrementi J, et al. Development of a high-throughput assay for aldosterone synthase inhibitors using high-performance liquid chromatography-tandem mass spectrometry. Anal Biochem. 2014;462:44–50.
   PubMed Web of Science ®Google Scholar
• Bureik M, Schiffler B, Hiraoka Y, et al. Functional expression of human mitochondrial CYP11B2 in fission yeast and identification of a new internal electron transfer protein, etp1. Biochemistry. 2002;41:2311–2321.
   PubMed Web of Science ®Google Scholar
• Dragan CA, Zearo S, Hannemann F, et al. Efficient conversion of 11-deoxycortisol to cortisol (hydrocortisone) by recombinant fission yeast Schizosaccharomyces pombe. FEMS Yeast Res. 2005;5:621–625.
   PubMed Web of Science ®Google Scholar
• Schiffler B, Bureik M, Reinle W, et al. The adrenodoxin-like ferredoxin of Schizosaccharomyces pombe mitochondria. J Inorg Biochem. 2004;98:1229–1237.
   PubMed Web of Science ®Google Scholar
• Ewen KM, Schiffler B, Uhlmann-Schiffler H, et al. The endogenous adrenodoxin reductase-like flavoprotein arh1 supports heterologous cytochrome P450-dependent substrate conversions in Schizosaccharomyces pombe. FEMS Yeast Res. 2008;8:432–441.
   PubMed Web of Science ®Google Scholar
• Hakki T, Zearo S, Dragan CA, et al. Coexpression of redox partners increases the hydrocortisone (cortisol) production efficiency in CYP11B1 expressing fission yeast Schizosaccharomyces pombe. J Biotechnol. 2008;133:351–359. Epub 2007 Oct 16.
   PubMed Web of Science ®Google Scholar
• Hakki T, Hubel K, Waldmann H, et al. The development of a whole-cell based medium throughput screening system for the discovery of human aldosterone synthase (CYP11B2) inhibitors: old drugs disclose new applications for the therapy of congestive heart failure, myocardial fibrosis and hypertension. J Steroid Biochem Mol Biol. 2011;125:120–128.
   PubMed Web of Science ®Google Scholar
• Schiffer L, Anderko S, Hobler A, et al. A recombinant CYP11B1 dependent Escherichia coli biocatalyst for selective cortisol production and optimization towards a preparative scale. Microb Cell Fact. 2015;14:25.
   PubMed Web of Science ®Google Scholar
• Belkina NV, Lisurek M, Ivanov AS, et al. Modelling of three-dimensional structures of cytochromes P450 11B1 and 11B2. J Inorg Biochem. 2001;87:197–207.
   PubMed Web of Science ®Google Scholar
• Ulmschneider S, Negri M, Voets M, et al. Development and evaluation of a pharmacophore model for inhibitors of aldosterone synthase (CYP11B2). Bioorg Med Chem Lett. 2006;16:25–30.
   PubMed Web of Science ®Google Scholar
• Böttner B, Schrauber H, Bernhardt R. Engineering a Mineralocorticoid- to a Glucocorticoid-synthesizing Cytochrome P450. J Biol Chem. 1996;271:8028–8033.
   PubMed Web of Science ®Google Scholar
• Hartmann RW, Muller U, Ehmer PB. Discovery of selective CYP11B2 (aldosterone synthase) inhibitors for the therapy of congestive heart failure and myocardial fibrosis. Eur J Med Chem. 2003;38:363–366.
   PubMed Web of Science ®Google Scholar
• Menard J, Pascoe L. Can the dextroenantiomer of the aromatase inhibitor fadrozole be useful for clinical investigation of aldosterone-synthase inhibition? J Hypertens. 2006;24:993–997.
   PubMed Web of Science ®Google Scholar
• Fiebeler A, Nussberger J, Shagdarsuren E, et al. Aldosterone synthase inhibitor ameliorates angiotensin II-induced organ damage. Circulation. 2005;111:3087–3094.
   PubMed Web of Science ®Google Scholar
• Lea WB, Kwak ES, Luther JM, et al. Aldosterone antagonism or synthase inhibition reduces end-organ damage induced by treatment with angiotensin and high salt. Kidney Int. 2009;75:936–944.
   PubMed Web of Science ®Google Scholar
• Minnaard-Huiban M, Emmen JM, Roumen L, et al. Fadrozole reverses cardiac fibrosis in spontaneously hypertensive heart failure rats: discordant enantioselectivity versus reduction of plasma aldosterone. Endocrinology. 2008;149:28–31.
   PubMed Web of Science ®Google Scholar
• Rigel DF, Fu F, Beil M, et al. Pharmacodynamic and pharmacokinetic characterization of the aldosterone synthase inhibitor FAD286 in two rodent models of hyperaldosteronism: comparison with the 11beta-hydroxylase inhibitor metyrapone. J Pharmacol Exp Ther. 2010;334:232–23.
   PubMed Web of Science ®Google Scholar
• Hille UE, Zimmer C, Vock CA, et al. First selective CYP11B1 inhibitors for the treatment of cortisol-dependent diseases. ACS Med Chem Lett. 2010;2:2–6.
   PubMed Web of Science ®Google Scholar
• Yin L, Lucas S, Maurer F, et al. Novel imidazol-1-ylmethyl substituted 1,2,5,6-tetrahydropyrrolo[3,2,1-ij]quinolin-4-ones as potent and selective CYP11B1 inhibitors for the treatment of Cushing’s syndrome. J Med Chem. 2012;55:6629–6633.
   PubMed Web of Science ®Google Scholar
• Menard J, Rigel DF, Watson C, et al. Aldosterone synthase inhibition: cardiorenal protection in animal disease models and translation of hormonal effects to human subjects. J Transl Med. 2014;12: 340.
   PubMed Web of Science ®Google Scholar
• Schumacher CD, Steele RE, Brunner HR, Aldosterone synthase inhibition for the treatment of hypertension and the derived mechanistic requirements for a new therapeutic strategy. J Hypertens. 2013;31:2085–2093.
   PubMed Web of Science ®Google Scholar
• Hoyt SB, Petrilli W, London C, et al. Discovery of Triazole CYP11B2 Inhibitors with in Vivo Activity in Rhesus Monkeys. ACS Med Chem Lett. 2015;6:861–865.
   PubMed Web of Science ®Google Scholar
• Martin RE, Aebi JD, Hornsperger B, et al. Discovery of 4-Aryl-5,6,7,8-tetrahydroisoquinolines as potent, selective, and orally active aldosterone synthase (CYP11B2) inhibitors: in vivo evaluation in rodents and Cynomolgus Monkeys. J Med Chem. 2015;2:8054–8065.
   Web of Science ®Google Scholar
• Azizi M, Amar L, Menard J. Aldosterone synthase inhibition in humans. Nephrol Dial Transplant. 2013;28:36–43.
   PubMed Web of Science ®Google Scholar
• Menard J, Watson C, Rebello S, et al. Hormonal and electrolyte response to the aldosterone synthase inhibitor LCI699 in sodium depleted healthy subjects. J Am Coll Cardiol. 2010;55:A61.E583.
   Google Scholar
• Amar L, Azizi M, Menard J, et al. Aldosterone synthase inhibition with LCI699: a proof-of-concept study in patients with primary aldosteronism. Hypertension. 2010;56:831–838.
   PubMed Web of Science ®Google Scholar
• Papillon JP, Adams CM, Hu QY, et al. Structure-activity relationships, pharmacokinetics, and in vivo activity of CYP11B2 and CYP11B1 inhibitors. J Med Chem. 2015;58:4749–4770.
   PubMed Web of Science ®Google Scholar
• Lucas S, Heim R, Ries C, et al. In vivo active aldosterone synthase inhibitors with improved selectivity: lead optimization providing a series of pyridine substituted 3,4-dihydro-1H-quinolin-2-one derivatives. J Med Chem. 2008;51:8077–8087.
   PubMed Web of Science ®Google Scholar
• Sonino N, Boscaro M. Medical therapy for Cushing’s disease. Endocrinol Metab Clin North Am. 1999;28:211–222.
   PubMed Web of Science ®Google Scholar
• Cai W, Counsell RE, Schteingart DE, et al. Adrenal proteins bound by a reactive intermediate of mitotane. Cancer Chemother Pharmacol. 1997;39:537–540.
   PubMed Web of Science ®Google Scholar
• Bertagna X, Pivonello R, Fleseriu M, et al. LCI699, a potent 11beta-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing’s disease: results from a multicenter, proof-of-concept study. J Clin Endocrinol Metab. 2014;99:1375–1383.
   PubMed Web of Science ®Google Scholar
• Rendic S, Guengerich FP. Survey of human oxidoreductases and cytochrome P450 enzymes involved in the metabolism of xenobiotic and natural chemicals. Chem Res Toxicol. 2015;28:38–42.
   PubMed Web of Science ®Google Scholar
• Yoetz-Kopelman T, Porat-Ophir C, Shacham-Diamand Y, et al. Whole-cell amperometric biosensor for screening of cytochrome P450 inhibitors. Sensor Actuat B Chem. 2016;223:392–399.
   Web of Science ®Google Scholar
• Delorme C, Piffeteau A, Viger A, et al. Inhibition of bovine cytochrome P-450(11 beta) by 18-unsaturated progesterone derivatives. Eur J Biochem. 1995;232:247–256.
   PubMedGoogle Scholar
• Melby JC, Azar ST, Delaney M, et al. 19-Nor-corticosteroids in genetic hypertension. Effects of inhibitors of 11beta,18,19-hydroxylase activity. J Steroid Biochem Mol Biol. 1993;45:13–18.
   PubMed Web of Science ®Google Scholar
• Azar ST, Melby JC, Griffing GT, et al. Antihypertensive effect of 19-acetylenic-deoxycorticosterone in inbred salt-sensitive rats. Am J Hypertens. 1992;5:372–377.
   PubMed Web of Science ®Google Scholar
• Adam O, Zimmer C, Hanke N, et al. Inhibition of aldosterone synthase (CYP11B2) by torasemide prevents atrial fibrosis and atrial fibrillation in mice. J Mol Cell Cardiol. 2015;85:140–150.
   PubMed Web of Science ®Google Scholar
• Robertson S, MacKenzie SM, Alvarez-Madrazo S, et al. MicroRNA-24 is a novel regulator of aldosterone and cortisol production in the human adrenal cortex. Hypertension. 2013;62:572–578.
   PubMed Web of Science ®Google Scholar
• Hwang KH, Carapito C, Bohmer S, et al. Proteome analysis of Schizosaccharomyces pombe by two-dimensional gel electrophoresis and mass spectrometry. Proteomics. 2006;6:4115–4129.
   PubMed Web of Science ®Google Scholar
• Bohmer S, Carapito C, Wilzewski B, et al. Analysis of aldosterone-induced differential receptor-independent protein patterns using 2D-electrophoresis and mass spectrometry. Biol Chem. 2006;387:917–929.
   PubMed Web of Science ®Google Scholar
• Zollner S, Hwang KH, Wilzewski B, et al. Aldosterone: from biosynthesis to non-genomic action onto the proteome. Steroids. 2008;73:966–972.
   PubMed Web of Science ®Google Scholar