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CYP17A1

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Target not currently curated in GtoImmuPdb

Target id: 1361

Nomenclature: CYP17A1

Family: CYP11, CYP17, CYP19, CYP20 and CYP21 families

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 508 10q24.32 CYP17A1 cytochrome P450 family 17 subfamily A member 1
Mouse - 507 19 38.97 cM Cyp17a1 cytochrome P450, family 17, subfamily a, polypeptide 1
Rat - 507 1q54 Cyp17a1 cytochrome P450, family 17, subfamily a, polypeptide 1
Previous and Unofficial Names Click here for help
Steroid 17-α-hydroxylase/17,20 lyase | cytochrome P450 17A1 | steroid 17-alpha hydroxylase | cytochrome P450, family 17, subfamily a, polypeptide 1 | cytochrome P450, family 17, subfamily A, polypeptide 1 | cytochrome P450
Database Links Click here for help
Alphafold P05093 (Hs), P27786 (Mm), P11715 (Rn)
BRENDA 1.14.14.19, 1.14.14.32
ChEMBL Target CHEMBL3522 (Hs), CHEMBL4430 (Rn)
DrugBank Target P05093 (Hs)
Ensembl Gene ENSG00000148795 (Hs), ENSMUSG00000003555 (Mm), ENSRNOG00000020035 (Rn)
Entrez Gene 1586 (Hs), 13074 (Mm), 25146 (Rn)
Human Protein Atlas ENSG00000148795 (Hs)
KEGG Enzyme 1.14.14.19, 1.14.14.32
KEGG Gene hsa:1586 (Hs), mmu:13074 (Mm), rno:25146 (Rn)
OMIM 609300 (Hs)
Orphanet ORPHA120963 (Hs)
Pharos P05093 (Hs)
SynPHARM 78807 (in complex with abiraterone)
82517 (in complex with galeterone)
UniProtKB P05093 (Hs), P27786 (Mm), P11715 (Rn)
Wikipedia CYP17A1 (Hs)
Enzyme Reaction Click here for help
EC Number: 1.14.14.19
EC Number: 1.14.14.32

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
levoketoconazole Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibition 7.4 pKi 5
⤷ pKi 7.4 (Ki 3.8x10-8 M) [5]
abiraterone-C6 oxime Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.8 pIC50 1
⤷ pIC50 7.8 (IC50 1.65x10-8 M) [1]
orteronel Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.7 pIC50 4
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [4]
Description: Measuring inhibition of Inhibition of 17,20-lyase activity of recombinant hCYP17A1
abiraterone Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.1 – 7.3 pIC50 2,6
⤷ pIC50 7.1 – 7.3 [2,6]
YXG-158 Small molecule or natural product Hs Inhibition 7.0 pIC50 8
⤷ pIC50 7.0 (IC50 1x10-7 M) [8]
seviteronel Small molecule or natural product Ligand has a PDB structure Hs Inhibition 6.2 – 7.2 pIC50 7
⤷ pIC50 7.2 (IC50 6.9x10-8 M) [7]
Description: Inhibition of hCYP17A1 lyase activity
pIC50 6.2 (IC50 6.7x10-7 M) [7]
Description: Inhibition of hCYP17A1 hydroxylase activity
galeterone Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.5 pIC50 3
⤷ pIC50 6.5 (IC50 3x10-7 M) [3]
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  46,XY disorder of sex development due to isolated 17, 20 lyase deficiency
Synonyms: 46 XY gonadal dysgenesis [Disease Ontology: DOID:14448]
Disease Ontology: DOID:14448
OMIM: 614279
Orphanet: ORPHA90796
Disease:  Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency
Synonyms: Congenital adrenal hyperplasia [Disease Ontology: DOID:12255]
Disease Ontology: DOID:12255
OMIM: 202110
Orphanet: ORPHA90793

References

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1. Fehl C, Vogt CD, Yadav R, Li K, Scott EE, Aubé J. (2018) Structure-Based Design of Inhibitors with Improved Selectivity for Steroidogenic Cytochrome P450 17A1 over Cytochrome P450 21A2. J Med Chem, 61 (11): 4946-4960. [PMID:29792703]

2. 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]

3. 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]

4. Kaku T, Hitaka T, Ojida A, Matsunaga N, Adachi M, Tanaka T, Hara T, Yamaoka M, Kusaka M, Okuda T et al.. (2011) Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer. Bioorg Med Chem, 19 (21): 6383-99. [PMID:21978946]

5. Njar VC, Kato K, Nnane IP, Grigoryev DN, Long BJ, Brodie AM. (1998) Novel 17-azolyl steroids, potent inhibitors of human cytochrome 17 alpha-hydroxylase-C17,20-lyase (P450(17) alpha): potential agents for the treatment of prostate cancer. J Med Chem, 41 (6): 902-12. [PMID:9526564]

6. 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]

7. Rafferty SW, Eisner JR, Moore WR, Schotzinger RJ, Hoekstra WJ. (2014) Highly-selective 4-(1,2,3-triazole)-based P450c17a 17,20-lyase inhibitors. Bioorg Med Chem Lett, 24 (11): 2444-7. [PMID:24775307]

8. Wang A, Luo X, Meng X, Lu Z, Chen K, Yang Y. (2023) Discovery of a Novel Bifunctional Steroid Analog, YXG-158, as an Androgen Receptor Degrader and CYP17A1 Inhibitor for the Treatment of Enzalutamide-Resistant Prostate Cancer. J Med Chem, 66 (14): 9972-9991. [PMID:37458396]

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