Table 8.

P450 11B2

Properties	References
Physiological substrate: 11-Deoxycorticosterone	(Denner et al. 1996; Coulter and Jaffe 1998; Roumen et al. 2011; 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 misused in sports), spironolactone, canrenone
Function: Aldosterone synthase, conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone (Figs. 4, 10)
Inhibition: Lower level of aldosterone, hypertension and heart failure treatment (Azizi et al. 2013; Karns et al. 2013)
Inhibitors: (Ehmer et al. 2002; Hartmann et al. 2003; Bureik et al. 2004; Muller-Vieira et al. 2005; Lucas, Heim, Negri, et al. 2008; Lucas, Heim, Ries, et al. 2008; Hakki et al. 2011; Papillon et al. 2015)
Drugs:
(R)- and (S)-Fadrozole a (Roumen et al. 2007)
(R)-Etomidate a (Roumen et al. 2007) Aminoglutethimide b (Schuster and Bernhardt 2007)
Aminoglutethimide b (Schuster and Bernhardt 2007)
Digoxin c (Kau et al. 2005)
Eplerone b (Moore et al. 2003; White et al. 2003)
Etomidate, iodometomidate, metomidate, fluoroetomidate c (Roumen et al. 2007; Hahner et al. 2008)
Fadrozole b (Muller-Vieira et al. 2005)
LCI699, silodrostat b (Amar et al. 2010; Karns et al. 2013))
Metyrapone (weak inhibitor) a (Roumen et al. 2007)
Miconazole, ketoconazole, clotrimazole, isoconazole a (Bureik et al. 2004; Hakki et al. 2011);
Mitotane b (Hakki et al. 2011)
Nifedipine c (Denner et al. 1996)
Phenelzineb (Hakki et al. 2011)
Staurosporine b (Bureik et al. 2002; Bureik et al. 2005)
Natural compounds:
Bufalin, cinobufagin c (Kau et al. 2012)
Chelerythrine, rottlerin b (Bureik et al. 2002)
Ellipticine b (Hakki et al. 2011)
Ouabain c (Kau et al. 2005)
Physiological compounds:
4-Androstene-3,17-dione b (Hakki et al. 2011)
Other compounds and drug candidates:
12-O-Tetradecanoyphorbol-13-acetate (TPA) c (LeHoux et al. 2001; LeHoux and Lefebvre 2004)
Phenylsulfinyl-3-(pyridin-3-yl)naphthalen-2-ols b (Grombein et al. 2015)
20-Hydroxyiminopregna-5,14-diene-3β-ol b (Ehmer et al. 2002)
1–3-Methylsulfonyl-DDE (at high concentrations)
4,5-Dihydro-[1,2,4]triazolo[4,3-a]quinolines b (Hu et al. 2015)
4-Anilino-pyrimidines b (Meguro et al. 2017)
Abiraterone analogues b (Pinto-Bazurco Mendieta et al. 2008)
Biphenylmethylene 4-pyridines b (Hu et al. 2010)
Calmidazolium b (Condon et al. 2002)
D, L-p-Chlorophenylalanine methyl ester b (Hakki et al. 2011)
FAD286 b (Brunssen et al. 2017)
Gö 6976 b (Bureik et al. 2002)
Heteroaryl-substituted dihydronaphthalenes and indenes b (Voets et al. 2006)
Heteroaryl-substituted naphthalenes b (Voets et al. 2005; Lucas, Heim, Negri, et al. 2008)
Imidazolylmethylenetetrahydronaphthalenes and imidazolylmethyleneindanes b (Ulmschneider et al. 2005)
Imidazolylmethylxanthones b (Gobbi et al. 2016)
Imidazopyridyl compounds (e.g. RO6836191) d (Bogman et al. 2017; Whitehead et al. 2017)
Indazole compounds b (Hoyt et al. 2017)
KN93 b (Condon et al. 2002)
Naphthalene based phenyl or benzyl derivatives a (Lucas, Heim, Negri, et al. 2008)
PA024 c (Suzuki et al. 2017)
Pyridine substituted 3,4-dihydro-1H-quinolin-2-one derivatives b (Lucas, Heim, Negri, et al. 2008)
Pyridyl- or isoquinolinyl-substituted indolines and indoles b (Yin et al. 2014)
Pyridyl substituted 4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines b (Hu et al. 2015)
Pyridyl substituted acenaphthene derivatives b (Ulmschneider et al. 2006)
Tetralins a (Ehmer et al. 2002; Muller-Vieira et al. 2005)
Triazoloquinolines b (Hu et al. 2015)
Turinabol c (Schiffer, Brixius-Anderko, et al. 2016)
Induction: affects sex hormone production, overproduction of aldosterone leads to hypertension and end-organ damage such as cardiac and renal hypertrophy
Inducers:
Drug(s):
BAYK 8644
Rifampicin e (Kim et al. 2013)
Telmisartan e (Matsuda et al. 2014)
Natural compounds:
3´,4´-Dimethoxyflavone e (Lin et al. 2006)
Calneuron 1 e (Kobuke et al. 2018)
Forskolin f (weak induction) (Denner et al. 1996)
Glucose (high concentrations) e (Shimada et al. 2017)
Physiological compounds:
Angiotensin IIg (Denner et al. 1996; Gennari-Moser et al. 2013;Matsuda, 2014, 59503}
Vascular endothelial growth factor (VEGF) g (Gennari-Moser et al. 2013)
Very low-density lipoprotein f (Tsai et al. 2017)
Other compounds:
2,4-Dibromophenol e (Ding et al. 2007)
3 -Methylsulfonyl-DDE (o, p´-DDT metabolite, at lower concentrations) e (Asp et al. 2010)
BAYK 8644 f (Denner et al. 1996)
Benzo[a]pyrene e (Keshava et al. 2005)
Brominated flame retardants e (e.g., 2,4-dibromophenol, pentabromophenol, 2,3,7,8-tetrabromodibenzofuran, TBDF) (Ding et al. 2007)
Calcium e (Shimada et al. 2017; Kobuke et al. 2018)
Organic sediment contaminants e (Blaha et al. 2006)
PD98059 e (LeHoux and Lefebvre 2004)
Polybrominated diphenyl ethers (e.g. 2´-OH-BDE-68) f (Song et al. 2008)
Polychlorinated and polybrominated biphenyls e (PCB- and PBD-39, −77, −126, −132, −156, and −169) e (Lin et al. 2006)
Potassiumf (Denner et al. 1996; Matsuda et al. 2014)
Tetrabromodibenzo-p-dioxin e (Ding et al. 2007)

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