Table 7.

P450 11B1

Properties	References
Physiological substrate: 11β-Deoxycortisol	(Denner et al. 1996; Coulter and Jaffe 1998; Parr et al. 2012; Bernhardt 2016; Pan et al. 2016; Schiffer, Brixius-Anderko, et al. 2016; Schiffer, Müller, et al. 2016)
Other substrates: Turinabol and metandienone (doping agents in sports), spironolactone, canrenone
Function: Steroid 11β- and 18-hydroxylation, cortisol formation (Figs. 4, 9)
Inhibition: Block synthesis of cortisol in Cushing’s syndrome and in chronic skin wounds, treating diseases caused by cortisol overproduction, interfere with the biosynthesis of aldosterone, possible application in treatment of adrenocortical carcinoma
Inhibitors: (Ehmer et al. 2002; Hartmann et al. 2003; Bureik et al. 2004; Muller-Vieira et al. 2005; Papillon et al. 2015)
Drugs:
Aminoglutethimide b (at high concentrations) (Vermeulen et al. 1983)
Canrenone, potassium canrenoate b (Cheng et al. 1976)
Cimetidine a (Kenyon et al. 1986)
Clotrimazole, miconazole, fluconazole a (Ayub and Levell 1989; Denner et al. 1995);
Etomidate a (Engelhardt and Weber 1994; Fassnacht et al. 2000)
Digoxin c (Kau et al. 2005)
(R)-Etomidate a (Roumen et al. 2007)
Fadrozole a (weak inhibitor) (Muller-Vieira et al. 2005)
(R)- and (S)-Fadrozole a (Roumen et al. 2007)
Iodometomidate, metomidate, fluoroetomidatec (Hahner et al. 2008)
Ketoconazoled (Ayub and Levell 1989; Denner et al. 1995; Johansson MK et al. 2002)
Metyrapone b (Fassnacht et al. 2000; Johansson MK et al. 2002; Roumen et al. 2007; Yin et al. 2012, Denner et al. 1995; Okahara et al. 1998)
Mitotane c (Lin CW et al. 2012)
Spironolactone b (Cheng et al. 1976; Denner et al. 1995)
Trilostane b (Johansson MK et al. 2002)
Turinabol c (Schiffer, Brixius-Anderko, et al. 2016)
Natural compounds:
Bufalin, cinobufagin b (Kau et al. 2012)
Chelerythrine, rottlerin b (Bureik, Zeeh, et al. 2002)
Ouabain c (Kau et al. 2005)
Physiological compounds:
Interferon-β c (van Koetsveld et al. 2013)
Other compounds, including drug candidates (only some examples are presented because of the large number of synthetic derivatives):
Abiraterone analogues a (Pinto-Bazurco Mendieta et al. 2008)
4,5-Dihydro-[1,2,4]triazolo[4,3-a]quinolines a (Hu et al. 2015)
Arylsulfonyltetrahydroquinolines b (Zhu et al. 2014)
Biphenylmethylene 4-pyridines b (Hu et al. 2010)
Gö 6976 b (Bureik, Zeeh, et al. 2002)
Heteroaryl-substituted dihydronaphthalenes and indenes b (Voets et al. 2006)
Heteroaryl-substituted naphthalenes b (Voets et al. 2005)
Imidazol-1-ylmethyl substituted 1,2,5,6-tetrahydropyrrolo[3,2,1-ij]quinolin-4-ones, pyridylmethyl pyridine compounds b (Yin et al. 2012)
Imidazolylmethylenetetrahydronaphthalenes and imidazolylmethyleneindanes b (Ulmschneider et al. 2005)
Imidazolylmethylxanthones b (Otton et al. 1993; Gobbi et al. 2016, 2017)
3-MeSO2-DDE d (Johansson MK et al. 2002)
3-Methylsulfonyl-DDE, MeSO2-PCBs (4-MeSO2-2,3,6,4´-tetrachlorobiphenyl, and 4-MeSO2-2,3,6,3´,4´-pentachlorobiphenyl b (Johansson M et al. 1998; Johansson MK et al. 2002);
5-(Phenoxymethyl)-1,3-dioxane analogs b (Schroeder et al. 2016)
1-Phenylsulfinyl-3-(pyridin-3-yl)naphthalen-2-ols b (Grombein et al. 2015)
Pyridyl substituted arylsulfonyltetrahydroquinolines b (Zhu et al. 2014)
Pyridylmethyl isoxazoles b (Emmerich et al. 2017)
Pyridylmethyl pyridine compounds b (Emmerich et al. 2018)
2,3,7,8-Tetrabromodibenzo-p-dioxin, TBDD c (Ding et al. 2007)
Tetralins b (Ehmer et al. 2002;Muller-Vieira et al. 2005)
Induction: Overproduction of cortisol is associated with Cushing’s syndrome and chronic wound diseases
Inducer:
Drugs:
Metyraponee (Coulter and Jaffe 1998)
Mitotanef (Lin CW et al. 2012)
Rifampicin f (Kim et al. 2013)
Natural compounds:
3´,4´-Dimethoxyflavone f (Lin TC et al. 2006)
Forskolin e (Denner et al. 1996)
Physiological compounds:
Adrenocorticotropic hormone g (Vukelic et al. 2011)
Angiotensin II e (Denner et al. 1996)
Dibutyryl cAMP e (Denner et al. 1996)
Other compounds:
2,3,7,8-Tetrabromodibenzo-p-dioxin, TBDD e (Ding et al. 2007)
3´,4´-Dimethoxyflavone f (Lin TC et al. 2006)
3-Methylsulfonyl-DDE (o, p´-DDT metabolite, at lower concentrations) f (at lower concentrations) (Asp et al. 2010)
Heteroaryl-substituted naphthalenes b (Voets et al. 2005)
Polychlorinated biphenyls (PCBs) −39, −77, −126, −132, −156, and −169) f (Lin TC et al. 2006)

Footnotes:

^acompetitive inhibition, ligand binding

^bdecreased/suppressed/inhibited activity/product formation

^creduced/suppressed mRNA and/or protein level/expression and activity

^dcompetitive inhibition, binding to enzyme active site

^eIncreased transcription/mRNA/protein expression/levels /and/or catalytic activity

^fUp-regulation of biosynthesis, increased expression of protein

^gIncreased activity, and/or increased product formation