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CYP19A1

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Target not currently curated in GtoImmuPdb

Target id: 1362

Nomenclature: CYP19A1

Abbreviated Name: Aromatase

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 2 503 15q21.2 CYP19A1 cytochrome P450 family 19 subfamily A member 1
Mouse 1 503 9 29.49 cM Cyp19a1 cytochrome P450, family 19, subfamily a, polypeptide 1
Rat - 508 8q24 Cyp19a1 cytochrome P450, family 19, subfamily a, polypeptide 1
Previous and Unofficial Names Click here for help
ARO | ARO1 | Cytochrome P450 19 aromatase | cytochrome P450 19A1 | cytochrome P450, family 19, subfamily a, polypeptide 1 | estrogen synthase | ArKO | cytochrome P450, family 19, subfamily A, polypeptide 1 | cytochrome P450
Database Links Click here for help
Alphafold P11511 (Hs), P28649 (Mm), P22443 (Rn)
BRENDA 1.14.14.14
ChEMBL Target CHEMBL1978 (Hs), CHEMBL3859 (Rn)
DrugBank Target P11511 (Hs)
Ensembl Gene ENSG00000137869 (Hs), ENSMUSG00000032274 (Mm), ENSRNOG00000000196 (Rn)
Entrez Gene 1588 (Hs), 13075 (Mm), 25147 (Rn)
Human Protein Atlas ENSG00000137869 (Hs)
KEGG Enzyme 1.14.14.14
KEGG Gene hsa:1588 (Hs), mmu:13075 (Mm), rno:25147 (Rn)
OMIM 107910 (Hs)
Orphanet ORPHA120969 (Hs)
Pharos P11511 (Hs)
SynPHARM 79391 (in complex with exemestane)
UniProtKB P11511 (Hs), P28649 (Mm), P22443 (Rn)
Wikipedia CYP19A1 (Hs)
Enzyme Reaction Click here for help
EC Number: 1.14.14.14

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
letrozole Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 10.7 pKi 9
⤷ pKi 10.7 (Ki 2x10-11 M) [9]
azalanstat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pKi 12
⤷ pKi 8.1 (Ki 7.6x10-9 M) [12]
exemestane Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibition 7.6 pKi 5
⤷ pKi 7.6 [5]
norendoxifen Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 pKi 8
⤷ pKi 6.3 (Ki 4.42x10-7 M) [8]
endoxifen Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.4 pKi 6
⤷ pKi 5.4 (Ki 4x10-6 M) [6]
testolactone Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 4.5 pKi 3
⤷ pKi 4.5 (Ki 3.5x10-5 M) [3]
fadrozole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.4 pIC50 2
⤷ pIC50 8.4 (IC50 4.5x10-9 M) [2]
letrozole Small molecule or natural product Approved drug Hs Inhibition 7.9 pIC50 1
⤷ pIC50 7.9 [1]
anastrozole Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 7.8 pIC50 4
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [4]
exemestane Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.4 pIC50 5
⤷ pIC50 7.4 (IC50 5.01x10-8 M) [5]
(2S,4S)-ketoconazole Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.4 pIC50 11
⤷ pIC50 5.4 [11]
endoxifen Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.2 pIC50 7
⤷ pIC50 5.2 (IC50 6x10-6 M) [7]
aminoglutethimide Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition - - 10
⤷ [10]
Inhibitor Comments
The reference for aminoglutethimide presents graphical data confirming the inhibition of CYP19A1 by this drug, but does present calculated Ki values [10].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Chemotaxis & migration
Immuno Process:  Immune system development
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Aromatase deficiency
OMIM: 613546
Orphanet: ORPHA91
Disease:  Aromatase excess syndrome
OMIM: 139300
Orphanet: ORPHA178345

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. Browne LJ, Gude C, Rodriguez H, Steele RE, Bhatnager A. (1991) Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease. J Med Chem, 34 (2): 725-36. [PMID:1825337]

3. 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]

4. 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]

5. 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]

6. Lu WJ, Desta Z, Flockhart DA. (2012) Tamoxifen metabolites as active inhibitors of aromatase in the treatment of breast cancer. Breast Cancer Res Treat, 131 (2): 473-81. [PMID:21390495]

7. Lu WJ, Xu C, Pei Z, Mayhoub AS, Cushman M, Flockhart DA. (2012) The tamoxifen metabolite norendoxifen is a potent and selective inhibitor of aromatase (CYP19) and a potential lead compound for novel therapeutic agents. Breast Cancer Res Treat, 133 (1): 99-109. [PMID:21814747]

8. Lv W, Liu J, Lu D, Flockhart DA, Cushman M. (2013) Synthesis of mixed (E,Z)-, (E)-, and (Z)-norendoxifen with dual aromatase inhibitory and estrogen receptor modulatory activities. J Med Chem, 56 (11): 4611-8. [PMID:23731360]

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. 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]

12. 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]

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