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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

Gene and Protein Information Click here for help
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, 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
BRENDA
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
SynPHARM
UniProtKB
Wikipedia
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 7
pKi 10.7 (Ki 2x10-11 M) [7]
azalanstat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pKi 10
pKi 8.1 (Ki 7.6x10-9 M) [10]
norendoxifen Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 pKi 6
pKi 6.3 (Ki 4.42x10-7 M) [6]
endoxifen Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.4 pKi 4
pKi 5.4 (Ki 4x10-6 M) [4]
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 1
pIC50 8.4 (IC50 4.5x10-9 M) [1]
anastrozole Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 7.8 pIC50 8
pIC50 7.8 (IC50 1.5x10-8 M) [8]
exemestane Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure 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 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.2 pIC50 5
pIC50 5.2 (IC50 6x10-6 M) [5]
aminoglutethimide Small molecule or natural product Approved drug Primary target of this compound 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].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes, IEA only
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GO:0002677 negative regulation of chronic inflammatory response IEA
GO:0010760 negative regulation of macrophage chemotaxis IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002677 negative regulation of chronic inflammatory response IEA
GO:0010760 negative regulation of macrophage chemotaxis IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0010760 negative regulation of macrophage chemotaxis IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:0030851 granulocyte differentiation IEP
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. 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]

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