CYP11, CYP17, CYP19, CYP20 and CYP21 families | Enzymes | IUPHAR/BPS Guide to IMMUNOPHARMACOLOGY

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CYP11, CYP17, CYP19, CYP20 and CYP21 families

CYP11, CYP17, CYP19, CYP20 and CYP21 families C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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The reactions catalysed by this family of cytochrome P450 monooxygenases are required for steroid biosynthesis.

Enzymes

1364

Targets of relevance to immunopharmacology are highlighted in blue

Cholesterol side-chain cleavage enzyme (CYP11A1) C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

1358

Nomenclature

CYP11A1

Common abbreviation

Cholesterol side-chain cleavage enzyme

Previous and unofficial names

Genes

CYP11A1 (Hs), Cyp11a1 (Mm), Cyp11a1 (Rn)

Ensembl ID

ENSG00000140459 (Hs), ENSMUSG00000032323 (Mm), ENSRNOG00000008074 (Rn)

UniProtKB AC

P05108 (Hs), Q9QZ82 (Mm), P14137 (Rn)

EC number

1.14.15.6

Inhibitors

(2S,4S)-ketoconazole pIC₅₀ 5.9 [12]

mitotane [7-8]

Comment

Converts cholesterol to pregnenolone plus 4-methylpentanal.

Steroid 11β-hydroxylase (CYP11B1) C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

1359

Nomenclature

CYP11B1

Common abbreviation

Steroid 11β-hydroxylase

Previous and unofficial names

Genes

CYP11B1 (Hs), Cyp11b1 (Mm), Cyp11b1 (Rn)

Ensembl ID

ENSG00000160882 (Hs), ENSMUSG00000075604 (Mm), ENSRNOG00000068909 (Rn)

UniProtKB AC

P15538 (Hs), P15393 (Rn)

EC number

1.14.15.4

Inhibitors

osilodrostat pIC₅₀ 8.5 [13]

metyrapone pIC₅₀ 7.8 [14]

(2S,4S)-ketoconazole pIC₅₀ 6.9 [12]

Comment

Converts deoxycortisone and 11-deoxycortisol to cortisone and cortisol, respectively. Loss-of-function mutations are associated with familial adrenal hyperplasia and hypertension.

Aldosterone synthase (CYP11B2) C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

1360

Nomenclature

CYP11B2

Common abbreviation

Aldosterone synthase

Previous and unofficial names

Genes

CYP11B2 (Hs), Cyp11b2 (Mm), Cyp11b2 (Rn)

Ensembl ID

ENSG00000179142 (Hs), ENSMUSG00000022589 (Mm), ENSRNOG00000030111 (Rn)

UniProtKB AC

P19099 (Hs), P15539 (Mm), P30099 (Rn), P30100 (Rn)

EC number

1.14.15.4

1.14.15.5

Inhibitors

osilodrostat pIC₅₀ 9.7 [13]

metyrapone pIC₅₀ 7.1 [14]

Comment

Converts corticosterone to aldosterone

CYP17A1 C Show summary »« Hide summary More detailed page go icon to follow link

Aromatase (CYP19A1) C Show summary »« Hide summary More detailed page go icon to follow link

CYP20A1 C Show summary »« Hide summary

Steroid 21-hydroxylase (CYP21A2) C Show summary »« Hide summary

Target Id

1364

Nomenclature

CYP21A2

Common abbreviation

Steroid 21-hydroxylase

Previous and unofficial names

Steroid 21-monooxygenase | Steroid 21-hydroxylase | cytochrome P450, family 21, subfamily A, polypeptide 2 | cytochrome P450, family 21, subfamily a, polypeptide 2 pseudogene | cytochrome P450

Genes

CYP21A2 (Hs), Cyp21a2-ps (Mm)

Ensembl ID

ENSG00000231852 (Hs), ENSMUSG00000092471 (Mm)

UniProtKB AC

P08686 (Hs)

EC number

1.14.14.16

Inhibitors

(2S,4S)-ketoconazole pIC₅₀ 5.4 [12] - Rat

Comment

Converts progesterone and 17α-hydroxyprogesterone to deoxycortisone and 11-deoxycortisol, respectively

References

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1. Bhatnagar AS, Häusler A, Schieweck K, Lang M, Bowman R. (1990) Highly selective inhibition of estrogen biosynthesis by CGS 20267, a new non-steroidal aromatase inhibitor. J Steroid Biochem Mol Biol, 37 (6): 1021-7. [PMID:2149502]

2. Covey DF, Hood WF. (1982) A new hypothesis based on suicide substrate inhibitor studies for the mechanism of action of aromatase. Cancer Res, 42 (8 Suppl): 3327s-3333s. [PMID:7083195]

3. Dukes M, Edwards PN, Large M, Smith IK, Boyle T. (1996) The preclinical pharmacology of "Arimidex" (anastrozole; ZD1033)--a potent, selective aromatase inhibitor. J Steroid Biochem Mol Biol, 58 (4): 439-45. [PMID:8903429]

4. Giudici D, Ornati G, Briatico G, Buzzetti F, Lombardi P, di Salle E. (1988) 6-Methylenandrosta-1,4-diene-3,17-dione (FCE 24304): a new irreversible aromatase inhibitor. J Steroid Biochem, 30 (1-6): 391-4. [PMID:3386266]

5. Haidar S, Ehmer PB, Barassin S, Batzl-Hartmann C, Hartmann RW. (2003) Effects of novel 17alpha-hydroxylase/C17, 20-lyase (P450 17, CYP 17) inhibitors on androgen biosynthesis in vitro and in vivo. J Steroid Biochem Mol Biol, 84 (5): 555-62. [PMID:12767280]

6. Handratta VD, Vasaitis TS, Njar VC, Gediya LK, Kataria R, Chopra P, Newman Jr D, Farquhar R, Guo Z, Qiu Y et al.. (2005) Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model. J Med Chem, 48 (8): 2972-84. [PMID:15828836]

7. Lehmann TP, Wrzesiński T, Jagodziński PP. (2013) The effect of mitotane on viability, steroidogenesis and gene expression in NCI‑H295R adrenocortical cells. Mol Med Rep, 7 (3): 893-900. [PMID:23254310]

8. Libè R, Fratticci A, Bertherat J. (2007) Adrenocortical cancer: pathophysiology and clinical management. Endocr Relat Cancer, 14 (1): 13-28. [PMID:17395972]

9. Mayhoub AS, Marler L, Kondratyuk TP, Park EJ, Pezzuto JM, Cushman M. (2012) Optimization of the aromatase inhibitory activities of pyridylthiazole analogues of resveratrol. Bioorg Med Chem, 20 (7): 2427-34. [PMID:22386564]

10. Payne EJ, Ingley E, Dick IM, Wilson SG, Bond CS, Prince RL. (2009) In vitro kinetic properties of the Thr201Met variant of human aromatase gene CYP19A1: functional responses to substrate and product inhibition and enzyme inhibitors. J Clin Endocrinol Metab, 94 (8): 2998-3002. [PMID:19470632]

11. Potter GA, Barrie SE, Jarman M, Rowlands MG. (1995) Novel steroidal inhibitors of human cytochrome P45017 alpha (17 alpha-hydroxylase-C17,20-lyase): potential agents for the treatment of prostatic cancer. J Med Chem, 38 (13): 2463-71. [PMID:7608911]

12. Rotstein DM, Kertesz DJ, Walker KA, Swinney DC. (1992) Stereoisomers of ketoconazole: preparation and biological activity. J Med Chem, 35 (15): 2818-25. [PMID:1495014]

13. Yin L, Hu Q, Emmerich J, Lo MM, Metzger E, Ali A, Hartmann RW. (2014) Novel pyridyl- or isoquinolinyl-substituted indolines and indoles as potent and selective aldosterone synthase inhibitors. J Med Chem, 57 (12): 5179-89. [PMID:24899257]

14. Zimmer C, Hafner M, Zender M, Ammann D, Hartmann RW, Vock CA. (2011) N-(Pyridin-3-yl)benzamides as selective inhibitors of human aldosterone synthase (CYP11B2). Bioorg Med Chem Lett, 21 (1): 186-90. [PMID:21129965]

How to cite this family page

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Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.