CYP19A1 | CYP11, CYP17, CYP19, CYP20 and CYP21 families | IUPHAR/BPS Guide to PHARMACOLOGY

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CYP19A1

Target not currently curated in GtoImmuPdb

Target id: 1362

Nomenclature: CYP19A1

Abbreviated Name: Aromatase

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

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 503 15q21 CYP19A1 cytochrome P450 family 19 subfamily A member 1
Mouse - 503 9 29.49 cM Cyp19a1 cytochrome P450, family 19, subfamily a, polypeptide 1
Rat - 508 8q23-q24 Cyp19a1 cytochrome P450
Previous and Unofficial Names
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
BRENDA
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
SynPHARM
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 1.14.14.14

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
letrozole Hs Inhibition 10.7 pKi 7
pKi 10.7 (Ki 2x10-11 M) [7]
azalanstat Hs Inhibition 8.1 pKi 10
pKi 8.1 (Ki 7.6x10-9 M) [10]
norendoxifen Hs Inhibition 6.3 pKi 6
pKi 6.3 (Ki 4.42x10-7 M) [6]
endoxifen Hs Inhibition 5.4 pKi 4
pKi 5.4 (Ki 4x10-6 M) [4]
testolactone Hs Inhibition 4.5 pKi 3
pKi 4.5 (Ki 3.5x10-5 M) [3]
fadrozole Hs Inhibition 8.4 pIC50 1
pIC50 8.4 (IC50 4.5x10-9 M) [1]
anastrozole Hs Inhibition 7.8 pIC50 8
pIC50 7.8 (IC50 1.5x10-8 M) [8]
exemestane Hs Inhibition 7.3 pIC50 2
pIC50 7.3 (IC50 5.01x10-8 M) [2]
Description: Inhibition of aromatase (CYP19A1) extracted to homogeneity from human placenta.
endoxifen Hs Inhibition 5.2 pIC50 5
pIC50 5.2 (IC50 6x10-6 M) [5]
aminoglutethimide Hs Inhibition - - 9
[9]
Inhibitor Comments
The reference for aminoglutethimide presents graphical data confirming the inhibition of CYP19A1 by this drug, but does present calculated Ki values [9].
Clinically-Relevant Mutations and Pathophysiology
Disease:  Aromatase deficiency
OMIM: 613546
Orphanet: ORPHA91
Disease:  Aromatase excess syndrome
OMIM: 139300
Orphanet: ORPHA178345

References

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1. 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]

2. Christiansen JS. (1985) Glomerular hyperfiltration in diabetes mellitus. Diabet. Med., 2 (4): 235-9. [PMID:2951074]

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. 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]

5. 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]

6. 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]

7. 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]

8. Muftuoglu Y, Mustata G. (2010) Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg. Med. Chem. Lett., 20 (10): 3050-64. [PMID:20413308]

9. 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]

10. 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 page

CYP11, CYP17, CYP19, CYP20 and CYP21 families: CYP19A1. Last modified on 28/01/2019. Accessed on 17/06/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1362.