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

1373

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

Target Id

1373

Nomenclature

CYP46A1

Common abbreviation

Cholesterol 24-hydroxylase

Previous and unofficial names

cytochrome P450, family 46, subfamily A, polypeptide 1 | cytochrome P450

Genes

CYP46A1 (Hs), Cyp46a1 (Mm), Cyp46a1 (Rn)

Ensembl ID

ENSG00000036530 (Hs), ENSMUSG00000021259 (Mm), ENSRNOG00000007147 (Rn)

UniProtKB AC

Q9Y6A2 (Hs), Q9WVK8 (Mm)

EC number

1.14.14.25

Inhibitors

soticlestat pIC₅₀ 8.4 [3]

Comment

Converts cholesterol to 24(S)-hydroxycholesterol.

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)

EC number

1.14.14.154

1.14.15.36

Inhibitors

azalanstat pK_i 9.1 [4]

compound 10 [PMID: 31663733] (Irreversible inhibition) pIC₅₀ >6.0 [1]

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. Nishi T, Kondo S, Miyamoto M, Watanabe S, Hasegawa S, Kondo S, Yano J, Watanabe E, Ishi T, Yoshikawa M et al.. (2020) Soticlestat, a novel cholesterol 24-hydroxylase inhibitor shows a therapeutic potential for neural hyperexcitation in mice. Sci Rep, 10 (1): 17081. [PMID:33051477]

4. 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 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.