Table 9.

P450 17A1

Properties	References
Physiological substrates; Progesterone, 17α-hydroxyprogesterone,17α-hydroxypregnenolone, 16α-hydroxyprogesterone	(Pikuleva et al. 2008; Petrunak et al. 2014; Pan et al. 2016; Gonzalez and Guengerich 2017; Yadav et al. 2017; Gonzalez et al. 2018)
Function: Biosynthesis of androgens and estrogens (cortisol), 16α-hydroxylase, 17α-hydroxylase, 17,20-lyase (Figs. 4, 11); controls the levels of mineralocorticoids influencing blood pressure, glucocorticoids involved in immune and stress responses, as well as androgens and estrogens involved in development and homeostasis of reproductive tissues
Inhibition: Lower androgen level and production in prostate cancer, treating diseases caused by cortisol overproduction; increases the pool of precursors for mineralocorticoid production and blocks P450 17A1-mediated production of glucocorticoids (Leroux 2005; Bird and Abbott 2016; Bonomo et al. 2016)
Inhibitors: (Ahmed 1999; Clement et al. 2003)
Drugs:
Abiraterone and analogsa (Pinto-Bazurco Mendieta et al. 2008; Ferraldeschi and de Bono 2013; Auchus R. J. et al. 2014; Petrunak et al. 2014; Yin and Hu 2014; Schroeder et al. 2016; Malikova et al. 2017)
Abiraterone, galeterone, seviteronel, orteronela (Yamaoka et al. 2012; Stein et al. 2014; Bird and Abbott 2016; Petrunak et al. 2017)
Azole drugsa (e.g., ketoconazole, liarozole—weak inhibitors) (Ayub and Levell 1989; Ideyama et al. 1998; Ahmed 1999; Clement et al. 2003; Bird and Abbott 2016) Ketoconazole (at high concentrations) (De Coster et al. 1986; Ayub and Levell 1989; Engelhardt and Weber 1994; Johansson et al. 2002)
Rifampicinb (Kim et al. 2013)
Valproic acidc (at high concentrations) (Glister et al. 2012)
Natural compounds:
1α,25-Dihydroxyvitamin D3 d (Lundqvist et al. 2010)
Daidzein, hesperitin, resveratrol d (Lin et al. 2014)
Polyphenols d (e.g., apigenin, aringenin, eriodictyol, genistein) d (Hasegawa et al. 2013)
Physiological compounds:
Bone morphogenetic protein 4 c (Rege et al. 2015)
Epidermal growth factorc (Doi et al. 2001)
Interferon-βc (van Koetsveld et al. 2013)
Other compounds, including drug candidates:
16- and 17-Azolyl steroids a (Njar et al. 1998)
5-(Phenoxymethyl)-1,3-dioxane analogs d (Schroeder et al. 2016)
6-Hydroxy-2,2´,4,4´-tetrabromodiphenyl ether d, bromodiphenyl ether-183 d (Canton et al. 2006; Song et al. 2008)
Biphenylmethylene 4-pyridines d (Hu et al. 2010)
Bisphenol A d (Niwa et al. 2001)
Imidazole, pyridine, 1,2,4- and 1,2,3-triazole, pyrazine, pyrimidine, pyrazole, oxazole, thiazole, isoxazole, 1,2,3,4- and 1,2,3,5-tetrazole and isothiazole containing compounds d (Bonomo et al. 2016)
Methoxy- and hydroxy-substituted methyleneimidazolyl biphenylsa (Hille et al. 2009)
α-Naphthoflavonec (Lin et al. 2014)
Nitrophenols d (Furuta et al. 2008)
Prochloraz d (Ohlsson et al. 2009)
Steroidal C-17 benzoazoles d (Handratta et al. 2005)
Vioxx (rofecoxib)-related lactones d (van Duursen et al. 2010)
YM116 d (Ideyama et al. 1998)
Induction: stimulation of androgen biosynthesis in man and risk of development of prostate cancer, or enhanced estrogen biosynthesis and risk of breast cancer
Inducers:
Drugs:
Cycloheximidee (Doi et al. 2001)
Valproic acidf (Nelson-DeGrave et al. 2004)
Natural compounds:
Retinoids e (Wickenheisser et al. 2005)
Forskolin e (Sawetawan et al. 1996; Nelson-DeGrave et al. 2004; Asif et al. 2006; Lin et al. 2014)
Physiological compounds:
Adrenocorticotropic hormone (ACTH) e (Di Blasio et al. 1987)
Cardiolipin g (Kisselev et al. 1999)
Cortisol e (Hsu et al. 2001; Auchus R. J. et al. 2014)
Insulin-like growth factors I and II e (Mesiano et al. 1997)
Other compounds:
PD98059 (MAPK kinase (MEK) inhibitor) e (Doi et al. 2001)
Polybrominated diphenyl ethers f (e.g. 2´-hydroxybromodiphenyl ether-68) (Song et al. 2008)

Footnotes:

^aCompetitive inhibition, ligand binding

^bCompetitive inhibition, binding to enzyme active site

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

^dDecreased/suppressed/inhibited activity/product formation

^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