CYP39, CYP46 and CYP51 families | Enzymes | IUPHAR/BPS Guide to PHARMACOLOGY

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CYP39, CYP46 and CYP51 families

CYP39, CYP46 and CYP51 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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Enzymes in this family are involved in cholesterol turnover and the biosynthesis of the crucial steroid precursor, lanosterol.

Enzymes

CYP39A1 C Show summary »« Hide summary

Target Id

1372

Nomenclature

CYP39A1

Previous and unofficial names

24-hydroxycholesterol 7-alpha-hydroxylase | oxysterol 7-alpha-hydroxylase | cytochrome P450, family 39, subfamily A, polypeptide 1 | cytochrome P450

Genes

CYP39A1 (Hs), Cyp39a1 (Mm), Cyp39a1 (Rn)

Ensembl ID

ENSG00000146233 (Hs), ENSMUSG00000023963 (Mm), ENSRNOG00000010519 (Rn)

UniProtKB AC

Q9NYL5 (Hs), Q9JKJ9 (Mm)

EC number

1.14.14.26

Comment

Converts 24-hydroxycholesterol to 7α,24-dihydroxycholesterol [2].

Cholesterol 24-hydroxylase (CYP46A1) C Show summary »« Hide summary

Lanosterol 14-α-demethylase (CYP51A1) C Show summary »« Hide summary

Target Id

1374

Nomenclature

CYP51A1

Common abbreviation

Lanosterol 14-α-demethylase

Previous and unofficial names

lanosterol 14-alpha demethylase | sterol 14-alpha demethylase | Cytochrom P450 Lanosterol 14 alpha-demethylase | cytochrome P450, family 51, subfamily A, polypeptide 1 | cytochrome P450

Genes

CYP51A1 (Hs), Cyp51 (Mm), Cyp51 (Rn)

Ensembl ID

ENSG00000001630 (Hs), ENSMUSG00000001467 (Mm), ENSRNOG00000007234 (Rn)

UniProtKB AC

Q16850 (Hs), Q8K0C4 (Mm), Q64654 (Rn)

Inhibitors

compound 10 [PMID: 31663733] (Irreversible inhibition) pK_d 7.1 [1]

azalanstat pK_i 9.1 [3]

Comment

Converts lanosterol to 4,4-dimethylcholesta-8.14.24-trienol. Proteins within the cholesterol pathway are being investigated as potential oncology targets. Small molecule inhibitors of human CYP51A1 have been reported to exhibit anti-proliferative activity in various cancer cells [1].

References

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1. Friggeri L, Hargrove TY, Wawrzak Z, Guengerich FP, Lepesheva GI. (2019) Validation of Human Sterol 14α-Demethylase (CYP51) Druggability: Structure-Guided Design, Synthesis, and Evaluation of Stoichiometric, Functionally Irreversible Inhibitors. J. Med. Chem., 62 (22): 10391-10401. [PMID:31663733]

2. Li-Hawkins J, Lund EG, Bronson AD, Russell DW. (2000) Expression cloning of an oxysterol 7alpha-hydroxylase selective for 24-hydroxycholesterol. J. Biol. Chem., 275 (22): 16543-9. [PMID:10748047]

3. Walker KA, Kertesz DJ, Rotstein DM, Swinney DC, Berry PW, So OY, Webb AS, Watson DM, Mak AY, Burton PM et al.. (1993) Selective inhibition of mammalian lanosterol 14 alpha-demethylase: a possible strategy for cholesterol lowering. J. Med. Chem., 36 (15): 2235-7. [PMID:8340925]

How to cite this family page

Database page citation (select format):

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2019) The Concise Guide to PHARMACOLOGY 2019/20: Enzymes. Br J Pharmacol. 176 Issue S1: S297-S396.