CYP19A1

Summary

CYP19A1 (cytochrome P450 family 19 subfamily A member 1, HGNC:2594) is a protein-coding gene on chromosome 15q21.2, encoding Aromatase (P11511). A cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and testosterone to the C18 estrogens, estrone and estradiol, respectively.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and catalyzes the last steps of estrogen biosynthesis. Mutations in this gene can result in either increased or decreased aromatase activity; the associated phenotypes suggest that estrogen functions both as a sex steroid hormone and in growth or differentiation. Alternative promoter use and alternative splicing results in multiple transcript variants that have different tissue specificities.

Source: NCBI Gene 1588 — RefSeq curated summary.

At a glance

• Gene–disease (curated): aromatase deficiency (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 53
• Clinical variants (ClinVar): 441 total — 37 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes — 40 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000103

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2594
Approved symbol	CYP19A1
Name	cytochrome P450 family 19 subfamily A member 1
Location	15q21.2
Locus type	gene with protein product
Status	Approved
Aliases	ARO, P-450AROM, CPV1, ARO1, CYAR, aromatase
Ensembl gene	ENSG00000137869
Ensembl biotype	protein_coding
OMIM	107910
Entrez	1588

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 16 protein_coding, 3 protein_coding_CDS_not_defined, 2 non_stop_decay, 2 retained_intron

ENST00000396402, ENST00000396404, ENST00000405011, ENST00000405913, ENST00000439712, ENST00000453807, ENST00000478421, ENST00000490076, ENST00000492852, ENST00000557858, ENST00000557934, ENST00000558066, ENST00000558328, ENST00000559646, ENST00000559653, ENST00000559878, ENST00000559980, ENST00000561066, ENST00000561075, ENST00000952752, ENST00000952753, ENST00000952754, ENST00000952755

RefSeq mRNA: 11 — MANE Select: NM_000103 NM_000103, NM_001347248, NM_001347249, NM_001347250, NM_001347251, NM_001347252, NM_001347253, NM_001347254, NM_001347255, NM_001347256, NM_031226

CCDS: CCDS10139

Canonical transcript exons

ENST00000396402 — 10 exons

Exon	Start	End
ENSE00001524808	51208057	51211056
ENSE00001548688	51338495	51338596
ENSE00001606124	51227779	51227933
ENSE00001621872	51242768	51242950
ENSE00001685378	51236859	51237009
ENSE00002571888	51222349	51222525
ENSE00003483454	51215070	51215232
ENSE00003531676	51215703	51215817
ENSE00003589550	51218541	51218655
ENSE00003683464	51212320	51212561

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 94.86.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.9182 / max 3686.1626, expressed in 74 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149912	3.5553	19
149901	0.0925	17
149903	0.0722	18
149894	0.0611	8
149908	0.0579	17
149902	0.0359	11
149900	0.0148	4
149898	0.0115	3
149893	0.0085	5
149899	0.0060	2

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	94.86	gold quality
right testis	UBERON:0004534	89.63	gold quality
left testis	UBERON:0004533	89.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.25	gold quality
testis	UBERON:0000473	84.94	gold quality
tibial nerve	UBERON:0001323	83.24	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.25	gold quality
germinal epithelium of ovary	UBERON:0001304	74.11	silver quality
subcutaneous adipose tissue	UBERON:0002190	71.16	gold quality
right ovary	UBERON:0002118	68.94	gold quality
right lobe of thyroid gland	UBERON:0001119	68.60	gold quality
left coronary artery	UBERON:0001626	68.60	gold quality
left ovary	UBERON:0002119	67.51	gold quality
ovary	UBERON:0000992	67.13	gold quality
coronary artery	UBERON:0001621	66.65	gold quality
left lobe of thyroid gland	UBERON:0001120	66.44	gold quality
right adrenal gland	UBERON:0001233	66.17	gold quality
buccal mucosa cell	CL:0002336	65.54	gold quality
diaphragm	UBERON:0001103	64.86	gold quality
thyroid gland	UBERON:0002046	64.78	gold quality
left adrenal gland	UBERON:0001234	64.63	gold quality
adrenal gland	UBERON:0002369	64.57	gold quality
skin of leg	UBERON:0001511	64.30	gold quality
tibial artery	UBERON:0007610	63.91	gold quality
popliteal artery	UBERON:0002250	63.86	gold quality
right adrenal gland cortex	UBERON:0035827	63.59	gold quality
right coronary artery	UBERON:0001625	63.33	gold quality
left adrenal gland cortex	UBERON:0035825	63.21	gold quality
descending thoracic aorta	UBERON:0002345	62.62	gold quality
aorta	UBERON:0000947	62.61	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	2064.64
E-MTAB-6701	yes	2004.98
E-HCAD-24	yes	1086.52
E-ANND-3	yes	4.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, AR, ASCL2, ATF2, BRCA1, CEBPA, CEBPB, CEBPD, CREB1, CREM, DMRT1, DNMT1, EGR2, EGR3, ESR1, ESRRA, ESRRG, FOS, FOXL2, GATA2, GATA4, GCM1, HIF1A, JUN, JUNB, JUND, LHX2, NCOR1, NFKB1, NFKB, NR0B1, NR0B2, NR1H4, NR2F1, NR2F2, NR2F6, NR3C1, NR4A1, NR4A2

miRNA regulators (miRDB)

105 targeting CYP19A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-3913-5P	99.78	67.26	968

Literature-anchored findings (GeneRIF, showing 40)

• Role of aromatase in endometrial disease. (PMID:11850203)
• Modulation of aromatase expression in human breast tissue. (PMID:11850205)
• Aromatase and COX-2 expression in human breast cancers. (PMID:11850206)
• Regulation of aromatase activity in bone-derived cells: possible role of mitogen-activated protein kinase. (PMID:11850208)
• Aromatase in atherosclerotic lesions of human aorta. (PMID:11850209)
• Molecular pharmacology of aromatase and its regulation by endogenous and exogenous agents. (PMID:11850210)
• Analysis of transcriptional regulation of human breast aromatase by in vitro and in vivo studies. (PMID:11850219)
• The potential role of estrogen in aromatase regulation in the breast. (PMID:11850220)
• Peptide inhibition of cytokine-stimulated aromatase activity in breast tissue fibroblasts. (PMID:11850221)
• Identification of the regulatory regions of the human aromatase P450 (CYP19) gene involved in placenta-specific expression. (PMID:11850222)
• Regulation of aromatase by nuclear receptors. (PMID:11850224)
• Tissue-specific expression of the human CYP19 (aromatase) gene in ovary and adipose tissue of transgenic mice. (PMID:11850225)
• 17alpha-methyl testosterone is a competitive inhibitor of aromatase activity in Jar choriocarcinoma cells and macrophage-like THP-1 cells in culture. (PMID:11850230)
• Phosphorylation processes mediate rapid changes of brain aromatase activity. (PMID:11850233)
• A comparative approach to structure-function studies of mammalian aromatases. (PMID:11850235)
• the effects of several paracrine and/or autocrine signaling pathways in the regulation of expression of aromatase in breast cancer cells identifies complex relationships (PMID:11897504)
• role in blood pressure (PMID:11903314)
• Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: implications in atherosclerosis (PMID:11904449)
• Association of the CYP19 gene polymorphism with risk of endometriosis in Japanese women. not significantly different between the groups. An increased frequency of the D/D genotype. 3 bp I/D polymorphism may be weakly associated with susceptibility. (PMID:11925378)
• regulation of expression in preadipocytes by liver receptor homologue-1 (PMID:11927588)
• aromatase expression is low in TIL but may have some functional significance for the estrogen-dependent growth of breast cancer tissue (PMID:11935306)
• both transactivation and down-regulation of estrogen receptor alpha by adrenal androgens increase with aromatase overexpression in transfected MCF7 cells (PMID:12160997)
• review: gene expression regulation of P450arom in Leydig cells and in germ cells and role in spermatogenesis (PMID:12161013)
• Spatially heterogeneous expression of aromatase P450 through promoter II is closely correlated with the level of steroidogenic factor-1 transcript in endometrioma tissues. (PMID:12161505)
• WT1 and DAX-1 inhibit its expression in human endometrial and endometriotic stromal cells (PMID:12213901)
• Promoter I.7 is a GATA-2-regulated endothelial promoter of the human CYP19 gene and may increase estrogen biosynthesis in vascular endothelial cells of breast cancer. (PMID:12351690)
• Aromatase (P450arom) catalyzes conversion of testosterone to estradiol, androstenedione to estrone, and 16a-hydroxylated dehydroepiandrosterone to estriol. Encoded by human CYP19 gene spanning about 123 kb with a coding region of 9 exons. Review. (PMID:12428207)
• releasing of aromatase of lung cancer tissue, which catalyzes androgen to change into estrogen, into external blood might be the major reason of the increase of estradiol and the decrease of testosterone in external blood. (PMID:12451990)
• Review. The P450arom plays a role in development, reproduction, sexual differentiation and behaviour, but also in bone and lipid metabolisms, brain functions and diseases such as breast and testicular tumors. (PMID:12462076)
• Review. Aromatase deficiency and its implications for reproduction and sex behavior are discussed. (PMID:12462077)
• C to A substitution in intron V, at position -3 of the splicing acceptor site before exon VI of the CYP19 gene causes of loss of aromatase. The mRNA leads to a frameshift and a premature stop codon 8 nucleotides downstream the end of exon V. (PMID:12466340)
• Human aromatase activity is critical for maintenance of early and mid pregnancy, in regulating parturition in late pregnancy, and for development of fetal gonadocytes and sexual differentiation of brain, especially the hypothalamic-gonadal axis. (PMID:12489562)
• cytochrome P450(aromatase) mRNA was not detected in the ovaries studied (PMID:12517592)
• Inhibition of IL-6+IL-6 soluble receptor-stimulated aromatase activity by the IL-6 antagonist, Sant 7, in breast tissue-derived fibroblasts (PMID:12592380)
• Data demonstrate the expression of aromatase mRNA and protein in human purified spermatozoa, and suggest that aromatase could be involved in the acquisition of sperm motility. (PMID:12606587)
• aromatase activity was up-regulated by activin stimulation through ActRIB in KGN cells. (PMID:12639945)
• results indicate that, in premenopausal women, a short microsatellite in the fourth intron of the CYP19 gene is associated with elevated androgens, perturbed regulation of the hypothalamic-pituitary-adrenal axis, and abdominal obesity (PMID:12690088)
• P-450AROM expression has been demonstrated in ejaculated immature sperm cells. (PMID:12705475)
• Vitamin D, testosterone, estrogens and glucocorticoids regulate CYP19 gene expression in human primary osteoblasts. Main promoter appears to be promoter I.4. (PMID:12720534)
• activating transcription factor 1(AP-1) motif is important in determining the up-regulatory effects induced by leptin on aromatase expression in MCF-7 breast cancer cells (PMID:12734209)

Cross-species orthologs

31 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyp19a1a	ENSDARG00000041348
mus_musculus	Cyp19a1	ENSMUSG00000032274
rattus_norvegicus	Cyp19a1	ENSRNOG00000000196
drosophila_melanogaster	Cyp4d1	FBGN0005670
drosophila_melanogaster	Cyp4d2	FBGN0011576
drosophila_melanogaster	Cyp4e2	FBGN0014469
drosophila_melanogaster	Cyp4c3	FBGN0015032
drosophila_melanogaster	Cyp4d8	FBGN0015033
drosophila_melanogaster	Cyp4e1	FBGN0015034
drosophila_melanogaster	Cyp4e3	FBGN0015035
drosophila_melanogaster	Cyp4ae1	FBGN0015036
drosophila_melanogaster	Cyp4p1	FBGN0015037
drosophila_melanogaster	Cyp4d14	FBGN0023541
drosophila_melanogaster	Cyp4s3	FBGN0030615
drosophila_melanogaster	Cyp4ac1	FBGN0031693
drosophila_melanogaster	Cyp4ac2	FBGN0031694
drosophila_melanogaster	Cyp4ac3	FBGN0031695
drosophila_melanogaster	Cyp4d21	FBGN0031925
drosophila_melanogaster	Cyp4ad1	FBGN0033292
drosophila_melanogaster	Cyp4p2	FBGN0033395
drosophila_melanogaster	Cyp4p3	FBGN0033397
drosophila_melanogaster	Cyp4aa1	FBGN0034053
drosophila_melanogaster	Cyp4d20	FBGN0035344
drosophila_melanogaster	Cyp312a1	FBGN0036778
caenorhabditis_elegans		WBGENE00007140
caenorhabditis_elegans		WBGENE00009226
caenorhabditis_elegans		WBGENE00010354
caenorhabditis_elegans		WBGENE00013381
caenorhabditis_elegans		WBGENE00016147
caenorhabditis_elegans		WBGENE00021200
caenorhabditis_elegans		WBGENE00021412

Paralogs (12): CYP4B1 (ENSG00000142973), CYP4V2 (ENSG00000145476), CYP4A22 (ENSG00000162365), CYP4F11 (ENSG00000171903), CYP4F22 (ENSG00000171954), CYP4F2 (ENSG00000186115), CYP4Z1 (ENSG00000186160), CYP4F12 (ENSG00000186204), CYP4X1 (ENSG00000186377), CYP4F8 (ENSG00000186526), CYP4F3 (ENSG00000186529), CYP4A11 (ENSG00000187048)

Protein

Protein identifiers

Aromatase — P11511 (reviewed: P11511)

Alternative names: CYPXIX, Cytochrome P-450AROM, Cytochrome P450 19A1, Estrogen synthase

All UniProt accessions (9): P11511, E7EPL6, E7EQ08, E9PGZ6, H0YK57, H0YKN1, H0YLP1, H0YLS2, H0YNJ7

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and testosterone to the C18 estrogens, estrone and estradiol, respectively. Catalyzes three successive oxidations of C19 androgens: two conventional oxidations at C19 yielding 19-hydroxy and 19-oxo/19-aldehyde derivatives, followed by a third oxidative aromatization step that involves C1-beta hydrogen abstraction combined with cleavage of the C10-C19 bond to yield a phenolic A ring and formic acid. Alternatively, the third oxidative reaction yields a 19-norsteroid and formic acid. Converts dihydrotestosterone to delta1,10-dehydro 19-nordihydrotestosterone and may play a role in homeostasis of this potent androgen. Also displays 2-hydroxylase activity toward estrone. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Widely expressed, including in adult and fetal brain, placenta, skin fibroblasts, adipose tissue and gonads.

Post-translational modifications. Phosphorylated in vitro by PKA and PKG/PRKG1. These phosphorylations inhibit the catalytic activity as measured by estrone synthesis from androstenedione (36% decrease for PKA and 30% for PKG/PRKG1).

Disease relevance. Aromatase excess syndrome (AEXS) [MIM:139300] An autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and isosexual precocity in females. The disease is caused by variants affecting the gene represented in this entry. Aromatase deficiency (AROD) [MIM:613546] A rare disease in which fetal androgens are not converted into estrogens due to placental aromatase deficiency. Thus, pregnant women exhibit a hirsutism, which spontaneously resolves after post-partum. At birth, female babies present with pseudohermaphroditism due to virilization of extern genital organs. In adult females, manifestations include delay of puberty, breast hypoplasia and primary amenorrhoea with multicystic ovaries. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Steroid hormone biosynthesis.

Similarity. Belongs to the cytochrome P450 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P11511-1	1	yes
P11511-2	2

RefSeq proteins (11): NP_000094, NP_001334177, NP_001334178, NP_001334179, NP_001334180, NP_001334181, NP_001334182, NP_001334183, NP_001334184, NP_001334185, NP_112503 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002401	Cyt_P450_E_grp-I	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050196	Cytochrome_P450_Monoox	Family

Pfam: PF00067

Enzyme classification (BRENDA):

• EC 1.14.14.14 — aromatase (BRENDA: 17 organisms, 13 substrates, 60 inhibitors, 5 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ANDROST-4-ENE-3,17-DIONE	0.0001–0.0002	2
16ALPHA-HYDROXYTESTOSTERONE	0.058	1
TESTOSTERONE	0.0002	1

Catalyzed reactions (Rhea), 9 shown:

• testosterone + 3 reduced [NADPH–hemoprotein reductase] + 3 O2 = 17beta-estradiol + formate + 3 oxidized [NADPH–hemoprotein reductase] + 4 H2O + 4 H(+) (RHEA:38191)
• androst-4-ene-3,17-dione + 3 reduced [NADPH–hemoprotein reductase] + 3 O2 = estrone + formate + 3 oxidized [NADPH–hemoprotein reductase] + 4 H2O + 4 H(+) (RHEA:38195)
• androst-4-ene-3,17-dione + reduced [NADPH–hemoprotein reductase] + O2 = 19-hydroxyandrost-4-ene-3,17-dione + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:38199)
• 19-hydroxyandrost-4-ene-3,17-dione + reduced [NADPH–hemoprotein reductase] + O2 = 19-oxo-androst-4-ene-3,17-dione + oxidized [NADPH–hemoprotein reductase] + 2 H2O + H(+) (RHEA:38203)
• 19-oxo-androst-4-ene-3,17-dione + reduced [NADPH–hemoprotein reductase] + O2 = estrone + formate + oxidized [NADPH–hemoprotein reductase] + H2O + 2 H(+) (RHEA:38207)
• estrone + reduced [NADPH–hemoprotein reductase] + O2 = 2-hydroxyestrone + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:47208)
• 17beta-hydroxy-5alpha-androstan-3-one + reduced [NADPH–hemoprotein reductase] + O2 = 17beta,19-dihydroxy-3-oxo-5alpha-androstanone + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:53200)
• 17beta,19-dihydroxy-3-oxo-5alpha-androstanone + reduced [NADPH–hemoprotein reductase] + O2 = 17beta-hydroxy-3,19-dioxo-5alpha-androstanone + oxidized [NADPH–hemoprotein reductase] + 2 H2O + H(+) (RHEA:53204)
• 17beta-hydroxy-3,19-dioxo-5alpha-androstanone + reduced [NADPH–hemoprotein reductase] + O2 = 17beta-hydroxy-3-oxo-19-nor-5alpha-androst-1-ene + formate + oxidized [NADPH–hemoprotein reductase] + H2O + 2 H(+) (RHEA:53276)

UniProt features (61 total): helix 22, strand 12, sequence variant 11, turn 7, binding site 3, transmembrane region 2, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
3S79	X-RAY DIFFRACTION	2.75
5JKV	X-RAY DIFFRACTION	2.75
3EQM	X-RAY DIFFRACTION	2.9
5JKW	X-RAY DIFFRACTION	3
5JL6	X-RAY DIFFRACTION	3
5JL7	X-RAY DIFFRACTION	3.1
5JL9	X-RAY DIFFRACTION	3.1
3S7S	X-RAY DIFFRACTION	3.21
4KQ8	X-RAY DIFFRACTION	3.29
4GL5	X-RAY DIFFRACTION	3.48
4GL7	X-RAY DIFFRACTION	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11511-F1	91.51	0.85

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 309; 374; 437 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-193144	Estrogen biosynthesis
R-HSA-211976	Endogenous sterols
R-HSA-5579030	Defective CYP19A1 causes AEXS

MSigDB gene sets: 345 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOZGIT_ESR1_TARGETS_DN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_GROWTH, GOBP_REGULATION_OF_HORMONE_LEVELS, REACTOME_ENDOGENOUS_STEROLS, GOBP_HORMONE_TRANSPORT, GOBP_KETONE_METABOLIC_PROCESS, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION

GO Biological Process (17): negative regulation of chronic inflammatory response (GO:0002677), steroid biosynthetic process (GO:0006694), estrogen biosynthetic process (GO:0006703), androgen catabolic process (GO:0006710), obsolete syncytium formation (GO:0006949), female gonad development (GO:0008585), negative regulation of macrophage chemotaxis (GO:0010760), sterol metabolic process (GO:0016125), female genitalia development (GO:0030540), mammary gland development (GO:0030879), response to estradiol (GO:0032355), uterus development (GO:0060065), prostate gland growth (GO:0060736), testosterone biosynthetic process (GO:0061370), positive regulation of estradiol secretion (GO:2000866), lipid metabolic process (GO:0006629), androgen metabolic process (GO:0008209)

GO Molecular Function (12): iron ion binding (GO:0005506), steroid hydroxylase activity (GO:0008395), electron transfer activity (GO:0009055), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen (GO:0016712), oxygen binding (GO:0019825), heme binding (GO:0020037), aromatase activity (GO:0070330), estrogen 2-hydroxylase activity (GO:0101021), monooxygenase activity (GO:0004497), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of steroid hormones	1
Cytochrome P450 - arranged by substrate type	1
Metabolic disorders of biological oxidation enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid metabolic process	3
monooxygenase activity	2
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	2
oxidoreductase activity	2
chronic inflammatory response	1
regulation of chronic inflammatory response	1
negative regulation of inflammatory response	1
lipid biosynthetic process	1
estrogen metabolic process	1
hormone biosynthetic process	1
steroid hormone biosynthetic process	1
steroid catabolic process	1
androgen metabolic process	1
hormone catabolic process	1
gonad development	1
development of primary female sexual characteristics	1
negative regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
negative regulation of macrophage migration	1
female sex differentiation	1
genitalia development	1
gland development	1
response to lipid	1
response to oxygen-containing compound	1
animal organ development	1
reproductive structure development	1
developmental process involved in reproduction	1
prostate gland development	1
organ growth	1
steroid biosynthetic process	1
ketone biosynthetic process	1
olefinic compound biosynthetic process	1
estradiol secretion	1
positive regulation of steroid hormone secretion	1
regulation of estradiol secretion	1
primary metabolic process	1
hormone metabolic process	1
transition metal ion binding	1
molecular_function	1

Protein interactions and networks

STRING

3681 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP19A1	ESR1	P03372	926
CYP19A1	ESR2	Q92731	923
CYP19A1	PGR	P06401	882
CYP19A1	STAR	P49675	877
CYP19A1	HSD3B1	P14060	861
CYP19A1	DHRS11	Q6UWP2	850
CYP19A1	AMH	P03971	845
CYP19A1	NR5A1	Q13285	834
CYP19A1	HSD17B1	P14061	822
CYP19A1	FSHR	P23945	813
CYP19A1	ERBB2	P04626	806
CYP19A1	AR	P10275	785
CYP19A1	LHCGR	P22888	782
CYP19A1	GNRH1	P01148	779
CYP19A1	CGNL1	Q0VF96	774

IntAct

7 interactions, top by confidence:

A	B	Type	Score
RC3H2	CYP19A1	psi-mi:“MI:0914”(association)	0.350
CYP19A1	H2AX	psi-mi:“MI:0914”(association)	0.350
CYP19A1	KLHL7	psi-mi:“MI:0914”(association)	0.350
CYP19A1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
A2M	TPP1	psi-mi:“MI:0403”(colocalization)	0.350

BioGRID (44): CYP19A1 (Affinity Capture-MS), CD109 (Affinity Capture-MS), H2AFX (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), NPLOC4 (Affinity Capture-MS), CYP19A1 (Affinity Capture-Western), CYP19A1 (Reconstituted Complex), CYP19A1 (Affinity Capture-MS), CYP19A1 (Affinity Capture-MS), UGT1A7 (Affinity Capture-MS), KLHL7 (Affinity Capture-MS), SGK3 (Affinity Capture-MS), CYP2S1 (Affinity Capture-MS), CYP51A1 (Affinity Capture-MS), PDZD8 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2RKY1, A0A7T9QPT0, B1NF18, B1NF19, B1NF20, B5UAQ8, B9DFU2, C7J3A2, I3QBP4, L7T720, L7T8H2, O46512, P05093, P05185, P0DKI7, P11511, P11715, P19100, P27786, P28649, P70687, Q0DBF4, Q29497, Q29605, Q2XVA1, Q50LH3, Q50LH4, Q54F47, Q54LT7, Q55AJ4, Q5QQX7, Q5Z5R4, Q5Z5R7, Q5Z5S6, Q64410, Q6JD68, Q6QHT9, Q8HYM9, Q8HYN0, Q8HYN1

Diamond homologs: A0A067DE75, A0A067ELB0, A0A067GFT7, A0A0B4L1W8, A0A0S2II38, A0A0U2U8U5, A0A140JWM8, A0A1D8QMD2, A0A1I9Q5Z0, A0A2H5AIX6, A0A3Q7HBJ5, A0A3Q7HS74, A0A5B8NBK9, A0A5B8ND26, A0A9E7S4M3, A0AAW1JA93, A0AAW1NEA3, A2A974, A2RRT9, A2Z212, A5BFI4, A9QNE7, F6H9N6, H2DH16, I1RE80, I7C6E8, I7CT85, K4CEE8, K4CI52, O14442, O18993, O35728, O46512, O48958, O81077, P08516, P0DXH8, P0DXI3, P0DXU9, P11511

SIGNOR signaling

22 interactions.

A	Effect	B	Mechanism
SRC	up-regulates	CYP19A1	phosphorylation
anastrozole	down-regulates	CYP19A1	“chemical inhibition”
exemestane	down-regulates	CYP19A1	“chemical inhibition”
letrozole	down-regulates	CYP19A1	“chemical inhibition”
CYP19A1	“up-regulates quantity”	17beta-estradiol	“chemical modification”
ESRRA	“up-regulates quantity by expression”	CYP19A1	“transcriptional regulation”
CREB1	“up-regulates quantity by expression”	CYP19A1	“transcriptional regulation”
FOXL2	“down-regulates quantity by repression”	CYP19A1	“transcriptional regulation”
NR5A1	“up-regulates quantity by expression”	CYP19A1	“transcriptional regulation”
NR5A2	“up-regulates quantity by expression”	CYP19A1	“transcriptional regulation”
JUN	“up-regulates quantity by expression”	CYP19A1	“transcriptional regulation”
FOS	“up-regulates quantity by expression”	CYP19A1	“transcriptional regulation”
CYP19A1	“up-regulates quantity”	estrone	“chemical modification”
CYP19A1	“down-regulates quantity”	testosterone	“chemical modification”
CYP19A1	“down-regulates quantity”	androst-4-ene-3,17-dione	“chemical modification”
aminoglutethimide	“down-regulates activity”	CYP19A1	“chemical inhibition”
testolactone	“down-regulates activity”	CYP19A1	“chemical inhibition”
formestane	“down-regulates activity”	CYP19A1	“chemical inhibition”
androsta-1,4,6-triene-3,17-dione	“down-regulates activity”	CYP19A1	“chemical inhibition”
ESR1	“down-regulates quantity by repression”	CYP19A1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

441 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	37
Likely pathogenic	21
Uncertain significance	89
Likely benign	243
Benign	33

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070106	NM_000103.4(CYP19A1):c.277G>T (p.Glu93Ter)	Pathogenic
1074615	NM_000103.4(CYP19A1):c.94_106dup (p.Leu36fs)	Pathogenic
1075120	NM_000103.4(CYP19A1):c.701_702insAA (p.Phe234fs)	Pathogenic
1076191	NM_000103.4(CYP19A1):c.1009C>T (p.Gln337Ter)	Pathogenic
1194713	NM_000103.4(CYP19A1):c.552T>G (p.Tyr184Ter)	Pathogenic
1356031	NM_000103.4(CYP19A1):c.716G>A (p.Trp239Ter)	Pathogenic
1368384	NM_000103.4(CYP19A1):c.433C>T (p.Arg145Ter)	Pathogenic
1436281	NM_000103.4(CYP19A1):c.502del (p.Leu168fs)	Pathogenic
1450839	NM_000103.4(CYP19A1):c.312_334del (p.Phe104fs)	Pathogenic
1459656	NC_000015.9:g.(?51529046)(51547938_?)del	Pathogenic
1460269	NM_000103.4(CYP19A1):c.596_597del (p.Thr198_Ser199insTer)	Pathogenic
2000107	NM_000103.4(CYP19A1):c.1058T>A (p.Leu353Ter)	Pathogenic
2023603	NM_000103.4(CYP19A1):c.365_366dup (p.Gln123fs)	Pathogenic
2025157	NM_000103.4(CYP19A1):c.795del (p.Ile266fs)	Pathogenic
2029138	NM_000103.4(CYP19A1):c.283_286del (p.Ile96fs)	Pathogenic
2079556	NM_000103.4(CYP19A1):c.87del (p.Leu30fs)	Pathogenic
2100852	NM_000103.4(CYP19A1):c.787dup (p.Arg263fs)	Pathogenic
2100917	NM_000103.4(CYP19A1):c.1028_1031del (p.Arg343fs)	Pathogenic
2419746	NM_000103.4(CYP19A1):c.876_877del (p.Asn295fs)	Pathogenic
2696892	NM_000103.4(CYP19A1):c.385G>T (p.Glu129Ter)	Pathogenic
2706864	NM_000103.4(CYP19A1):c.563del (p.Val187_Leu188insTer)	Pathogenic
2765535	NM_000103.4(CYP19A1):c.652dup (p.Gln218fs)	Pathogenic
2809977	NM_000103.4(CYP19A1):c.220dup (p.Cys74fs)	Pathogenic
3243895	NC_000015.9:g.(?51529036)(51529226_?)del	Pathogenic
3243896	NC_000015.9:g.(?51503005)(51504778_?)del	Pathogenic
3243897	NC_000015.9:g.(?51507247)(51520150_?)del	Pathogenic
3243898	NC_000015.9:g.(?51510718)(51514742_?)del	Pathogenic
3633001	NM_000103.4(CYP19A1):c.1282C>T (p.Gln428Ter)	Pathogenic
3641712	NM_000103.4(CYP19A1):c.693del (p.Asp232fs)	Pathogenic
4731326	NM_000103.4(CYP19A1):c.1275del (p.Arg425fs)	Pathogenic

SpliceAI

1914 predictions. Top by Δscore:

Variant	Effect	Δscore
15:51212318:A:AC	donor_gain	1.0000
15:51212319:C:CC	donor_gain	1.0000
15:51212319:CATT:C	donor_gain	1.0000
15:51212382:T:TA	donor_gain	1.0000
15:51212386:T:TA	donor_gain	1.0000
15:51212557:CTCAC:C	acceptor_gain	1.0000
15:51212558:TCAC:T	acceptor_gain	1.0000
15:51212559:CAC:C	acceptor_gain	1.0000
15:51212559:CACC:C	acceptor_gain	1.0000
15:51212560:AC:A	acceptor_gain	1.0000
15:51212561:CC:C	acceptor_gain	1.0000
15:51212562:C:A	acceptor_loss	1.0000
15:51212562:C:CC	acceptor_gain	1.0000
15:51212564:G:GC	acceptor_gain	1.0000
15:51212571:C:CT	acceptor_gain	1.0000
15:51212572:A:T	acceptor_gain	1.0000
15:51212574:A:AC	acceptor_gain	1.0000
15:51212574:A:C	acceptor_gain	1.0000
15:51215064:TCTTA:T	donor_loss	1.0000
15:51215065:CTTA:C	donor_loss	1.0000
15:51215066:TTA:T	donor_loss	1.0000
15:51215067:TACCA:T	donor_loss	1.0000
15:51215068:A:AC	donor_gain	1.0000
15:51215068:A:C	donor_loss	1.0000
15:51215069:C:CC	donor_gain	1.0000
15:51215069:C:CG	donor_loss	1.0000
15:51215228:CGTTT:C	acceptor_gain	1.0000
15:51215238:C:CT	acceptor_gain	1.0000
15:51215239:A:T	acceptor_gain	1.0000
15:51215241:T:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000017099 (15:51277150 G>A,T), RS1000022414 (15:51240843 T>G), RS1000039499 (15:51233911 C>G,T), RS1000046812 (15:51339474 C>T), RS1000090098 (15:51324278 T>A), RS1000104469 (15:51310027 C>T), RS1000130105 (15:51282877 T>C), RS1000137935 (15:51240574 G>A), RS1000154481 (15:51294876 G>A), RS1000171713 (15:51214810 G>T), RS1000221920 (15:51260315 A>C,G), RS1000233502 (15:51247527 T>C), RS1000235933 (15:51261238 C>G,T), RS1000239266 (15:51261565 A>G), RS1000280810 (15:51307424 A>G)

Disease associations

OMIM: gene MIM:107910 | disease phenotypes: MIM:613546, MIM:139300

GenCC curated gene-disease

Disease	Classification	Inheritance
aromatase deficiency	Definitive	Autosomal recessive
aromatase excess syndrome	Moderate	Autosomal dominant

Mondo (4): aromatase deficiency (MONDO:0013301), pulmonary disease, chronic obstructive, susceptibility to (MONDO:0100167), aromatase excess syndrome (MONDO:0007690), primary ovarian failure (MONDO:0005387)

Orphanet (3): Aromatase deficiency (Orphanet:91), Aromatase excess syndrome (Orphanet:178345), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000026	Male hypogonadism
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000061	Ambiguous genitalia, female
HP:0000098	Tall stature
HP:0000138	Ovarian cyst
HP:0000771	Gynecomastia
HP:0000786	Primary amenorrhea
HP:0000815	Hypergonadotropic hypogonadism
HP:0000855	Insulin resistance
HP:0000858	Irregular menstruation
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000956	Acanthosis nigricans
HP:0001397	Hepatic steatosis
HP:0001510	Growth delay
HP:0001513	Obesity
HP:0001620	Abnormally high-pitched voice
HP:0002050	Macroorchidism, postpubertal
HP:0002230	Generalized hirsutism
HP:0002653	Bone pain
HP:0002663	Delayed epiphyseal ossification
HP:0002750	Delayed skeletal maturation
HP:0002857	Genu valgum
HP:0003077	Hyperlipidemia
HP:0003251	Male infertility
HP:0003502	Mild short stature
HP:0003577	Congenital onset
HP:0003782	Eunuchoid habitus

GWAS associations

53 associations (top):

Study	Trait	p-value
GCST000611_8	Height	7.000000e-07
GCST000817_102	Height	2.000000e-09
GCST000827_2	Cerebrospinal fluid AB1-42 levels	2.000000e-09
GCST001553_4	Estradiol levels	5.000000e-07
GCST001859_26	Thiazide-induced adverse metabolic effects in hypertensive patients	8.000000e-06
GCST001885_6	Height	5.000000e-10
GCST001973_1	Menarche (age at onset)	4.000000e-07
GCST002195_1	Hormone measurements	8.000000e-28
GCST002195_5	Hormone measurements	7.000000e-31
GCST002199_6	Follicle stimulating hormone levels	2.000000e-16
GCST002647_109	Height	1.000000e-15
GCST002702_71	Height	3.000000e-31
GCST002794_18	Airway wall thickness	2.000000e-06
GCST003485_14	Response to fenofibrate (HDL cholesterol levels)	5.000000e-07
GCST003524_7	Endometrial cancer	5.000000e-13
GCST003525_6	Endometrial endometrioid carcinoma	2.000000e-13
GCST004361_4	Estrone/androstenedione ratio in resected early stage-receptor positive breast cancer	4.000000e-06
GCST005348_192	Total body bone mineral density	2.000000e-08
GCST005827_1	Estrone levels	6.000000e-23
GCST005827_2	Estrone levels	2.000000e-22
GCST005828_1	Estradiol levels	8.000000e-30
GCST006016_26	Serum alkaline phosphatase levels	5.000000e-09
GCST006288_165	Heel bone mineral density	1.000000e-15
GCST006288_166	Heel bone mineral density	1.000000e-06
GCST006288_332	Heel bone mineral density	2.000000e-09
GCST006288_437	Heel bone mineral density	7.000000e-23
GCST006288_438	Heel bone mineral density	8.000000e-06
GCST006464_22	Endometrial cancer	3.000000e-14
GCST006465_32	Endometrial cancer (endometrioid histology)	2.000000e-10
GCST006979_1021	Heel bone mineral density	2.000000e-28

EFO canonical traits (18, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004697	estradiol measurement
EFO:0004703	age at menarche
EFO:0004768	follicle stimulating hormone measurement
EFO:0006898	airway wall thickness measurement
EFO:0007805	HDL cholesterol change measurement
EFO:1001514	endometrial endometrioid carcinoma
EFO:0007970	estrone measurement
EFO:0007972	androstenedione measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0009270	heel bone mineral density
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007986	reticulocyte count
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C537436	Aromatase deficiency (supp.)
C000591739	familial gynecomastia, due to increased aromatase activity (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1978 (SINGLE PROTEIN), CHEMBL6066122 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

40 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,363,718 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL106	FLUCONAZOLE	4	58,942
CHEMBL1200374	EXEMESTANE	4	72,530
CHEMBL1397	POSACONAZOLE	4	541
CHEMBL1399	ANASTROZOLE	4	89,972
CHEMBL1405	ESTRONE	4	36,722
CHEMBL1444	LETROZOLE	4	81,122
CHEMBL1571	TESTOLACTONE	4	57,527
CHEMBL157101	KETOCONAZOLE	4	75,361
CHEMBL185	FLUOROURACIL	4	299,469
CHEMBL3099695	OSILODROSTAT	4	347
CHEMBL386630	TESTOSTERONE	4	129,997
CHEMBL488	AMINOGLUTETHIMIDE	4	74,271
CHEMBL56367	NIMESULIDE	4	25,455
CHEMBL91	MICONAZOLE	4	45,914
CHEMBL1093458	ENDOXIFEN	3	523
CHEMBL165	RESVERATROL	3	60,144
CHEMBL367149	DOCONEXENT	3	63,817
CHEMBL460026	ICOSAPENT	3	60,180
CHEMBL50	QUERCETIN	3	74,559
CHEMBL132530	FORMESTANE	2
CHEMBL151	LUTEOLIN	2
CHEMBL169	URSOLIC ACID	2
CHEMBL2105261	PLOMESTANE	2
CHEMBL224060	VOROZOLE	2
CHEMBL267476	LINOLEIC ACID	2
CHEMBL275638	FLAVONE	2
CHEMBL27769	STANOLONE	2
CHEMBL286738	IROSUSTAT	2
CHEMBL287677	DEXFADROSTAT	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

17 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10046	Other	3	hdl cholesterol;letrozole;triglycerides	Breast Neoplasms;Menopause
rs1008805	Other	3	HMG-CoA reductase inhibitors;letrozole	Breast Neoplasms;Menopause
rs1008805	Toxicity	3	anastrozole	Breast Neoplasms
rs1062033	Other	3	HMG-CoA reductase inhibitors;letrozole	Breast Neoplasms;Menopause
rs2236722	Efficacy	3	capecitabine;fluorouracil	Metastatic neoplasm
rs2289105	Other	3	hdl cholesterol;letrozole;triglycerides	Breast Neoplasms;Menopause
rs3759811	Other	3	letrozole	Breast Neoplasms;Menopause
rs4646	Other	3	letrozole	Breast Neoplasms;Menopause
rs4646	Efficacy	3	tamoxifen	Breast Neoplasms;Menopause
rs4646	Efficacy	3	tamoxifen	Breast Neoplasms
rs4775936	Other	3	letrozole	Breast Neoplasms;Menopause
rs6493497	Toxicity	3	exemestane;letrozole	Breast Neoplasms
rs6493497	Efficacy	3	anastrozole;exemestane;letrozole	Breast Neoplasms
rs700518	Other	3	letrozole	Breast Neoplasms;Menopause
rs7176005	Toxicity	3	exemestane	Breast Neoplasms
rs727479	Efficacy	3	anastrozole	Breast Neoplasms
rs749292	Other	3	letrozole	Breast Neoplasms;Menopause

PharmGKB variants

15 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4646	CYP19A1	3	5.75	3	letrozole;tamoxifen
rs10046	CYP19A1	3	2.75	1	hdl cholesterol;letrozole;triglycerides
rs700518	CYP19A1	3	1.50	1	letrozole
rs700519	CYP19A1		0.00	0
rs749292	CYP19A1	3	1.50	1	letrozole
rs1008805	CYP19A1	3	2.50	2	HMG-CoA reductase inhibitors;letrozole;anastrozole
rs1062033	CYP19A1	3	1.25	1	HMG-CoA reductase inhibitors;letrozole
rs2236722	CYP19A1	3	0.00	1	capecitabine;fluorouracil
rs2289105	CYP19A1	3	2.75	1	hdl cholesterol;letrozole;triglycerides
rs3759811	CYP19A1	3	1.50	1	letrozole
rs4775936	CYP19A1	3	1.50	1	letrozole
rs6493497	CYP19A1, GLDN	3	5.00	2	exemestane;letrozole;anastrozole;exemestane;letrozole
rs7176005	CYP19A1, GLDN	3	3.00	1	exemestane
rs727479	CYP19A1	3	2.00	1	anastrozole
rs730154	CYP19A1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — CYP11, CYP17, CYP19, CYP20 and CYP21 families

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
fadrozole	Inhibition	8.35	pIC50
azalanstat	Inhibition	8.12	pKi
letrozole	Inhibition	7.9	pIC50
anastrozole	Inhibition	7.82	pIC50
exemestane	Inhibition	7.6	pKi
norendoxifen	Inhibition	6.35	pKi
(2S,4S)-ketoconazole	Inhibition	5.4	pIC50
endoxifen	Inhibition	5.22	pIC50
testolactone	Inhibition	4.46	pKi

Binding affinities (BindingDB)

397 measured of 479 human assays (481 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Neoflavonoid, 8	KI	0.00182 nM
Neoflavonoid, 7	KI	0.00216 nM
Neoflavonoid, 9	KI	0.00256 nM
5,7-dihydroxy-3-(4-methoxyphenyl)-4H-chromen-4-one	EC50	0.00334 nM
Neoflavonoid, 11	KI	0.00425 nM
Neoflavonoid, 19	KI	0.00597 nM
Neoflavonoid, 10	KI	0.00838 nM
Neoflavonoid, 20	KI	0.0118 nM
4-{(4-chloro-3-hydroxyphenyl)methylamino}benzonitrile	IC50	0.18 nM
4-{(4-hydroxy-3-iodophenyl)methylamino}benzonitrile	IC50	0.33 nM
4-({[3-hydroxy-4-(trifluoromethyl)phenyl]methyl}(4H-1,2,4-triazol-4-yl)amino)benzonitrile	IC50	0.4 nM
4-{(4-bromophenyl)methylamino}benzonitrile	IC50	0.5 nM
4-{(4-bromo-3-hydroxyphenyl)methylamino}benzonitrile	IC50	0.5 nM
4-{(3-chloro-4-hydroxy-5-methoxyphenyl)methylamino}benzonitrile	IC50	0.51 nM
4-[(R)-(3-bromo-4-hydroxyphenyl)(1H-1,2,4-triazol-1-yl)methyl]benzonitrile	IC50	0.6 nM
4-{(4-fluoro-3-hydroxyphenyl)methylamino}benzonitrile	IC50	0.6 nM
(5-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}-2-fluorophenyl) sulfamate	IC50	0.77 nM
YM511-based dual aromatase-sulfatase inhibitor (DASI) 7	IC50	0.82 nM
4-({[4-hydroxy-3-(trifluoromethyl)phenyl]methyl}(4H-1,2,4-triazol-4-yl)amino)benzonitrile	IC50	0.88 nM
(2-chloro-5-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl) sulfamate	IC50	0.92 nM
4-{(3-bromo-4-hydroxyphenyl)methylamino}benzonitrile	IC50	1.1 nM
4-{(3-hydroxy-4-methoxyphenyl)methylamino}benzonitrile	IC50	1.2 nM
(4-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}-2-iodophenyl) sulfamate	IC50	1.5 nM
4-[(3-bromo-4-hydroxyphenyl)(1H-1,2,4-triazol-1-yl)methyl]benzonitrile	IC50	1.8 nM
(2-chloro-4-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl) sulfamate	IC50	2.3 nM
3-[4-(1,2-Dihydro-1,5-dimethyl-2-phenyl-3-oxo-3H-pyrazol-4-ylcarbonyl]isoxazole (16)	IC50	2.3 nM
3-[(R)-1H-imidazol-1-yl(4-nitrophenyl)methyl]-4H-chromen-4-one	IC50	2.3 nM
4-{(3-chloro-4-hydroxyphenyl)methylamino}benzonitrile	IC50	2.5 nM
4,4 -(1H-1,2,4-triazol-1-ylmethanediyl)dibenzonitrile	IC50	2.8 nM
4-{(4-hydroxy-3-methoxyphenyl)methylamino}benzonitrile	IC50	2.8 nM
4-{(3-hydroxyphenyl)methylamino}benzonitrile	IC50	2.8 nM
(2-chloro-4-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}-6-methoxyphenyl) sulfamate	IC50	2.9 nM
4-{(3-fluoro-4-hydroxyphenyl)methylamino}benzonitrile	IC50	2.9 nM
{2-bromo-4-[(4-cyanophenyl)(1H-1,2,4-triazol-1-yl)methyl]phenyl} sulfamate	IC50	3 nM
(8S)-2,8,15-trimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-14-one	KI	3.1 nM
{2-bromo-4-[(R)-(4-cyanophenyl)(1H-1,2,4-triazol-1-yl)methyl]phenyl} sulfamate	IC50	3.2 nM
2-Chloro-4-[4-(1,2-dihydro-1,5-dimethyl-2-phenyl-3-oxo-3H-pyrazol-4-yl)thiazole (26)	IC50	3.3 nM
3-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-5H-thiazolo[2,3-b]quinazolin-5-one (21)	IC50	3.4 nM
4-[(S)-(3-bromo-4-hydroxyphenyl)(1H-1,2,4-triazol-1-yl)methyl]benzonitrile	IC50	3.4 nM
(2S,6S,15S)-6-hydroxy-2-(hydroxymethyl)-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-7-en-14-one	KI	3.4 nM
2-Hydroxy-4-([4-(1,2-dihydro-1,5-dimethyl-2-phenyl-3-oxo-3H-pyrazol-4-yl)thiazole (25)	IC50	3.5 nM
1-Phenyl-3-[4-(1,2-Dihydro-1,5-dimethyl-2-phenyl-3-oxo-3H-pyrazol-4-ylcarbonyl]-4-thiocyanatopyrazole (13)	IC50	3.7 nM
2-[4-(1,2-Dihydro-1,5-dimethyl-2-phenyl-3-oxo-3H-pyrazol-4-yl]-1,3,4-thiazolo[3,2-a]-1,3-quinazolin-2-one (10b)	IC50	3.9 nM
(2-bromo-5-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl) sulfamate	IC50	3.9 nM
3-[4-(3-amino-1,2-benzoxazol-4-yl)phenyl]-1-(4-methylphenyl)urea	IC50	4 nM
3-[4-(3-amino-1,2-benzoxazol-4-yl)phenyl]-1-(4-fluorophenyl)urea	IC50	4 nM
2-[4-(1,2-Dihydro-1,5-dimethyl-2-phenyl-3-oxo-3H-pyrazol-4-yl)]-1,3,4-thidiazole[3,2-a]-1,3-quinazoline-2-imine (10a)	IC50	4.1 nM
4-[4-(1,2-Dihydro-1,5-dimethyl-2-phenyl-3-oxo-3H-pyrazol-4-ylcarbonyl)]-5-phenylamino-1,3-dithiole-2-imine (7)	IC50	4.6 nM
(8R)-8-ethyl-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-diene-5,14-dione	KI	4.7 nM
3-[4-(3-amino-1,2-benzoxazol-4-yl)phenyl]-1-(3-nitrophenyl)urea	IC50	5 nM

ChEMBL bioactivities

3937 potent at pChembl≥5 of 4477 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL4639677
11.00	IC50	0.01	nM	CHEMBL4632445
10.82	IC50	0.015	nM	CHEMBL1672978
10.82	IC50	0.015	nM	CHEMBL1672980
10.74	IC50	0.018	nM	CHEMBL1672979
10.70	IC50	0.02	nM	CHEMBL5438093
10.70	Ki	0.02	nM	LETROZOLE
10.55	IC50	0.02799	nM	CHEMBL5425028
10.52	IC50	0.03	nM	FADROZOLE HYDROCHLORIDE
10.43	IC50	0.037	nM	CHEMBL310735
10.35	Ki	0.045	nM	CHEMBL73279
10.31	IC50	0.049	nM	CHEMBL305205
10.30	IC50	0.05	nM	CHEMBL1672975
10.30	IC50	0.05	nM	CHEMBL73993
10.30	Ki	0.05	nM	FADROZOLE
10.22	IC50	0.06	nM	CHEMBL1629804
10.22	Ki	0.06	nM	CHEMBL1957214
10.05	IC50	0.09	nM	CHEMBL5203413
10.05	IC50	0.08872	nM	CHEMBL5396048
10.00	IC50	0.1	nM	CHEMBL3623231
10.00	IC50	0.1	nM	CHEMBL5408436
10.00	IC50	0.1	nM	CHEMBL597416
10.00	IC50	0.1	nM	CHEMBL1672974
9.96	IC50	0.11	nM	CHEMBL197650
9.96	IC50	0.11	nM	CHEMBL70436
9.92	IC50	0.12	nM	CHEMBL592131
9.92	IC50	0.12	nM	CHEMBL108425
9.92	IC50	0.12	nM	CHEMBL4520995
9.92	IC50	0.1199	nM	CHEMBL3623231
9.92	IC50	0.12	nM	CHEMBL307581
9.89	IC50	0.13	nM	CHEMBL308537
9.89	Ki	0.13	nM	ANASTROZOLE
9.85	IC50	0.14	nM	CHEMBL5401648
9.85	Ki	0.14	nM	CHEMBL73367
9.82	IC50	0.15	nM	CHEMBL597808
9.82	IC50	0.15	nM	CHEMBL198291
9.82	IC50	0.15	nM	CHEMBL1672977
9.80	Ki	0.16	nM	FORMESTANE
9.80	IC50	0.16	nM	CHEMBL5436996
9.80	IC50	0.16	nM	CHEMBL72228
9.74	IC50	0.18	nM	CHEMBL226946
9.74	Ki	0.18	nM	CHEMBL74339
9.72	IC50	0.19	nM	CHEMBL307643
9.70	IC50	0.2	nM	CHEMBL3623232
9.70	IC50	0.2	nM	CHEMBL4465348
9.70	IC50	0.2	nM	CHEMBL592852
9.70	IC50	0.2	nM	CHEMBL597606
9.68	IC50	0.2099	nM	CHEMBL5406734
9.68	IC50	0.21	nM	CHEMBL1672976
9.66	IC50	0.2198	nM	CHEMBL5416513

PubChem BioAssay actives

3583 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
7-methoxy-4-(3,4,5-trimethoxyphenyl)-3,4-dihydrochromen-2-one	1799798: Aromatase Assay from Article 10.1111/j.1747-0285.2012.01439.x: “Neoflavonoids and Tetrahydroquinolones as Possible Cancer Chemopreventive Agents.”	ki	<0.0001	uM
3-(imidazol-1-ylmethyl)-6-pent-2-ynoxyxanthen-9-one	1863225: Inhibition of aromatase in human JEG-3 cells using Androst-4-ene-3,17-dione as substrate incubated for 1 hr and measured by BCA assay	ic50	<0.0001	uM
1-(imidazol-1-ylmethyl)-3-pent-2-ynoxyxanthen-9-one	1863225: Inhibition of aromatase in human JEG-3 cells using Androst-4-ene-3,17-dione as substrate incubated for 1 hr and measured by BCA assay	ic50	<0.0001	uM
4-[2-(1H-indol-4-yl)-2-(triazol-1-yl)ethyl]benzonitrile	2022023: Inhibition of aromatase in human placental microsomes using [1beta-3H]AD as substrate incubated for 14 mins by liquid scintillation method	ic50	<0.0001	uM
4-[3-(3-bromo-4-hydroxyphenyl)-1-(1,2,4-triazol-1-yl)propyl]benzonitrile	2022019: Inhibition of human aromatase using ASD as substrate pre-incubated for 5 mins followed by substrate addition and measured after 16 hrs by UV/vis-spectrophotometry	ic50	<0.0001	uM
5,7-dimethoxy-4-(3,4,5-trimethoxyphenyl)-3,4-dihydrochromen-2-one	1799798: Aromatase Assay from Article 10.1111/j.1747-0285.2012.01439.x: “Neoflavonoids and Tetrahydroquinolones as Possible Cancer Chemopreventive Agents.”	ki	<0.0001	uM
8-(3,4,5-trimethoxyphenyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]chromen-6-one	1799798: Aromatase Assay from Article 10.1111/j.1747-0285.2012.01439.x: “Neoflavonoids and Tetrahydroquinolones as Possible Cancer Chemopreventive Agents.”	ki	<0.0001	uM
(6S)-6,10,13-trimethyl-1,2,3,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one	53556: In vitro inhibition of cytochrome P450 19A1 in human placental microsomes	ic50	<0.0001	uM
(6R)-6,10,13-trimethyl-1,2,3,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one	53556: In vitro inhibition of cytochrome P450 19A1 in human placental microsomes	ic50	<0.0001	uM
(17S)-10,13-dimethyl-2,3,6,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-ol	54047: Apparent inhibition constant (Ki) against Cytochrome P450 19A1	ki	<0.0001	uM
8-(4-hydroxy-3,5-dimethoxyphenyl)-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]quinolin-6-one	1799798: Aromatase Assay from Article 10.1111/j.1747-0285.2012.01439.x: “Neoflavonoids and Tetrahydroquinolones as Possible Cancer Chemopreventive Agents.”	ki	<0.0001	uM
8-(3,4,5-trimethoxyphenyl)-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]quinolin-6-one	1799798: Aromatase Assay from Article 10.1111/j.1747-0285.2012.01439.x: “Neoflavonoids and Tetrahydroquinolones as Possible Cancer Chemopreventive Agents.”	ki	<0.0001	uM
Letrozole	650843: Competitive inhibition of human aromatase using dibenzylfluorescein substrate after 10 mins preincubation measured every 10 sec for 5 mins by Michaelis-Menten and Dixon plot analysis	ki	<0.0001	uM
8-(4-hydroxy-3,5-dimethoxyphenyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]chromen-6-one	1799798: Aromatase Assay from Article 10.1111/j.1747-0285.2012.01439.x: “Neoflavonoids and Tetrahydroquinolones as Possible Cancer Chemopreventive Agents.”	ki	<0.0001	uM
[2,6-dimethoxy-4-(6-oxo-7,8-dihydro-[1,3]dioxolo[4,5-g]chromen-8-yl)phenyl] acetate	1799798: Aromatase Assay from Article 10.1111/j.1747-0285.2012.01439.x: “Neoflavonoids and Tetrahydroquinolones as Possible Cancer Chemopreventive Agents.”	ki	<0.0001	uM
[2-bromo-4-[[4-cyano-3-phenyl-N-(1,2,4-triazol-4-yl)anilino]methyl]phenyl] sulfamate	570240: Inhibition of aromatase in human JEG-3 cells using [1beta-3H]androstenedione after 1 hr by scintillation spectrometry	ic50	<0.0001	uM
[2-chloro-4-[[4-cyano-3-phenyl-N-(1,2,4-triazol-4-yl)anilino]methyl]phenyl] sulfamate	570240: Inhibition of aromatase in human JEG-3 cells using [1beta-3H]androstenedione after 1 hr by scintillation spectrometry	ic50	<0.0001	uM
[4-[[4-cyano-3-(4-methoxyphenyl)-N-(1,2,4-triazol-4-yl)anilino]methyl]phenyl] sulfamate	570240: Inhibition of aromatase in human JEG-3 cells using [1beta-3H]androstenedione after 1 hr by scintillation spectrometry	ic50	<0.0001	uM
1-[(4-fluorophenyl)-(6-methoxy-1-benzofuran-2-yl)methyl]-1,2,4-triazole	1863225: Inhibition of aromatase in human JEG-3 cells using Androst-4-ene-3,17-dione as substrate incubated for 1 hr and measured by BCA assay	ic50	0.0001	uM
4-[(6-methoxy-1-benzofuran-2-yl)-(1,2,4-triazol-1-yl)methyl]benzonitrile	1863225: Inhibition of aromatase in human JEG-3 cells using Androst-4-ene-3,17-dione as substrate incubated for 1 hr and measured by BCA assay	ic50	0.0001	uM
(8R,9S,10R,13S,14S)-10,13-dimethyl-1,2,3,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one	53556: In vitro inhibition of cytochrome P450 19A1 in human placental microsomes	ic50	0.0001	uM
[2-bromo-4-[3-(4-cyanophenyl)-3-(1,2,4-triazol-1-yl)propyl]phenyl] sulfamate	1250238: Inhibition of aromatase in human JEG-3 cells using [1beta-3H]androstenedione as substrate after 1 hr by scintillation spectrometry	ic50	0.0001	uM
4-[(6-but-2-ynoxy-1-benzofuran-2-yl)-(1,2,4-triazol-1-yl)methyl]benzonitrile	1863225: Inhibition of aromatase in human JEG-3 cells using Androst-4-ene-3,17-dione as substrate incubated for 1 hr and measured by BCA assay	ic50	0.0001	uM
4-[2-(2,6-difluoro-4-hydroxyphenyl)ethyl-(4H-pyrazol-4-yl)amino]benzonitrile	2022019: Inhibition of human aromatase using ASD as substrate pre-incubated for 5 mins followed by substrate addition and measured after 16 hrs by UV/vis-spectrophotometry	ic50	0.0001	uM
4-[(5-bromo-6-hydroxynaphthalen-2-yl)methyl-(1,2,4-triazol-4-yl)amino]benzonitrile	2022019: Inhibition of human aromatase using ASD as substrate pre-incubated for 5 mins followed by substrate addition and measured after 16 hrs by UV/vis-spectrophotometry	ic50	0.0001	uM
4-[(4-bromophenyl)methyl-(1,2,4-triazol-4-yl)amino]benzonitrile	1249539: Inhibition of aromatase in human placental microsome	ic50	0.0001	uM
Anastrozole	650843: Competitive inhibition of human aromatase using dibenzylfluorescein substrate after 10 mins preincubation measured every 10 sec for 5 mins by Michaelis-Menten and Dixon plot analysis	ki	0.0001	uM
2-(3-chloro-4-hydroxyphenyl)-4-(1,2,4-triazol-1-ylmethyl)benzonitrile	1249546: Inhibition of aromatase (unknown origin) expressed in JEG-3 cells	ic50	0.0001	uM
2-[3-(3-chloro-4-hydroxyphenyl)-5-(1,2,4-triazol-1-ylmethyl)phenyl]-2-methylpropanenitrile	461809: Inhibition of aromatase in human JEG3 cells by scintillation spectrometry	ic50	0.0001	uM
(6S)-6-ethyl-10,13-dimethyl-1,2,3,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one	53556: In vitro inhibition of cytochrome P450 19A1 in human placental microsomes	ic50	0.0001	uM
(6S)-6-methoxy-10,13-dimethyl-1,2,3,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one	53556: In vitro inhibition of cytochrome P450 19A1 in human placental microsomes	ic50	0.0001	uM
(6R)-6-hydroxy-10,13-dimethyl-1,2,3,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one	53556: In vitro inhibition of cytochrome P450 19A1 in human placental microsomes	ic50	0.0001	uM
(6R)-6-methoxy-10,13-dimethyl-1,2,3,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one	53556: In vitro inhibition of cytochrome P450 19A1 in human placental microsomes	ic50	0.0001	uM
(6R)-6,10,13-trimethyl-2,3,6,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-ol	54047: Apparent inhibition constant (Ki) against Cytochrome P450 19A1	ki	0.0001	uM
[2-chloro-4-[2-cyano-5-(1,2,4-triazol-1-ylmethyl)phenyl]phenyl] sulfamate	1249546: Inhibition of aromatase (unknown origin) expressed in JEG-3 cells	ic50	0.0001	uM
[4-[5-[(4-bromophenyl)methyl-(1,2,4-triazol-4-yl)amino]-2-cyanophenyl]phenyl] sulfamate	570240: Inhibition of aromatase in human JEG-3 cells using [1beta-3H]androstenedione after 1 hr by scintillation spectrometry	ic50	0.0001	uM
[4-[5-[benzyl(1,2,4-triazol-4-yl)amino]-2-cyanophenyl]phenyl] sulfamate	570240: Inhibition of aromatase in human JEG-3 cells using [1beta-3H]androstenedione after 1 hr by scintillation spectrometry	ic50	0.0001	uM
[4-[[4-cyano-3-phenyl-N-(1,2,4-triazol-4-yl)anilino]methyl]-2-fluorophenyl] sulfamate	570240: Inhibition of aromatase in human JEG-3 cells using [1beta-3H]androstenedione after 1 hr by scintillation spectrometry	ic50	0.0001	uM
4-pyridin-3-yl-2-pyridin-4-yl-1,3-thiazole	650843: Competitive inhibition of human aromatase using dibenzylfluorescein substrate after 10 mins preincubation measured every 10 sec for 5 mins by Michaelis-Menten and Dixon plot analysis	ki	0.0001	uM
(8R,9S,10R,13S,14S)-4-hydroxy-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17-dione	1937758: Binding affinity to aromatase (unknown origin) assessed as inhibition constant	ki	0.0002	uM
[4-[[4-cyano-N-(1,2,4-triazol-4-yl)anilino]methyl]-3-fluorophenyl] sulfamate	1599430: Inhibition of aromatase (unknown origin)	ic50	0.0002	uM
4-[(4-chloro-3-hydroxyphenyl)methyl-(1,2,4-triazol-4-yl)amino]benzonitrile	1798417: Aromatase Inhibition Assay from Article 10.1021/jm061462b: “Dual aromatase-steroid sulfatase inhibitors.”	ic50	0.0002	uM
[4-[3-(4-cyanophenyl)-3-(1,2,4-triazol-1-yl)propyl]phenyl] sulfamate	2022019: Inhibition of human aromatase using ASD as substrate pre-incubated for 5 mins followed by substrate addition and measured after 16 hrs by UV/vis-spectrophotometry	ic50	0.0002	uM
4-[2-(3-bromo-4-hydroxyphenyl)-1-(1,2,4-triazol-1-yl)ethyl]benzonitrile	2022019: Inhibition of human aromatase using ASD as substrate pre-incubated for 5 mins followed by substrate addition and measured after 16 hrs by UV/vis-spectrophotometry	ic50	0.0002	uM
4-[3-(4-hydroxyphenyl)-1-(1,2,4-triazol-1-yl)propyl]benzonitrile	2022019: Inhibition of human aromatase using ASD as substrate pre-incubated for 5 mins followed by substrate addition and measured after 16 hrs by UV/vis-spectrophotometry	ic50	0.0002	uM
2-phenyl-4-(1,2,4-triazol-1-ylmethyl)benzonitrile	461809: Inhibition of aromatase in human JEG3 cells by scintillation spectrometry	ic50	0.0002	uM
2-(4-hydroxyphenyl)-4-(1,2,4-triazol-1-ylmethyl)benzonitrile	461809: Inhibition of aromatase in human JEG3 cells by scintillation spectrometry	ic50	0.0002	uM
(6S)-10,13-dimethyl-6-propyl-1,2,3,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one	53556: In vitro inhibition of cytochrome P450 19A1 in human placental microsomes	ic50	0.0002	uM
(6S)-6-hydroxy-10,13-dimethyl-1,2,3,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one	53556: In vitro inhibition of cytochrome P450 19A1 in human placental microsomes	ic50	0.0002	uM
[(6S)-10,13-dimethyl-17-oxo-1,2,3,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-6-yl] acetate	53556: In vitro inhibition of cytochrome P450 19A1 in human placental microsomes	ic50	0.0002	uM

CTD chemical–gene interactions

341 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, increases reaction, decreases methylation, decreases expression, decreases reaction (+6 more)	19
Estradiol	increases activity, affects cotreatment, increases expression, increases phosphorylation, decreases reaction (+7 more)	19
Letrozole	decreases reaction, increases activity, increases abundance, increases expression, decreases activity	18
Colforsin	increases activity, increases abundance, decreases reaction, increases expression, affects cotreatment (+1 more)	18
Atrazine	increases abundance, affects cotreatment, affects reaction, increases expression, increases reaction (+5 more)	14
Tetrachlorodibenzodioxin	increases expression, affects reaction, decreases expression, affects activity, affects cotreatment (+3 more)	12
formestane	decreases activity, decreases abundance, decreases reaction, increases activity, affects chemical synthesis (+1 more)	9
Resveratrol	decreases activity, increases expression, decreases reaction, increases reaction, decreases expression	8
Anastrozole	decreases activity	8
Androstenedione	affects reaction, decreases activity, decreases metabolic processing, increases activity, decreases reaction (+4 more)	8
Estrogens	affects chemical synthesis, increases chemical synthesis, affects binding, decreases activity	8
Testosterone	affects abundance, affects metabolic processing, affects cotreatment, increases expression, increases reaction (+3 more)	8
Dinoprostone	increases activity, increases expression, affects reaction, affects binding, increases reaction (+1 more)	8
tributyltin	affects binding, affects metabolic processing, increases metabolic processing, decreases expression, affects cotreatment (+5 more)	7
prochloraz	decreases activity, increases activity, affects cotreatment, increases expression	7
exemestane	decreases activity	7
Benzo(a)pyrene	affects cotreatment, decreases expression, affects methylation, increases expression	6
Valproic Acid	increases reaction, increases activity, decreases activity, affects expression, decreases reaction (+3 more)	6
Genistein	decreases reaction, increases activity, increases expression, affects cotreatment, decreases activity (+1 more)	6
Aromatase Inhibitors	decreases response to substance, affects binding, decreases activity, increases mutagenesis	6
Fulvestrant	decreases reaction, increases expression, increases activity, decreases activity	5
Aminoglutethimide	increases expression, affects chemical synthesis, affects metabolic processing, decreases activity, increases activity (+1 more)	5
Dexamethasone	increases reaction, decreases expression, increases expression, increases activity	5
Estrone	increases chemical synthesis, affects binding, decreases activity, decreases chemical synthesis, decreases abundance (+3 more)	5
Quercetin	decreases expression, increases activity, increases expression, decreases activity	5
Tamoxifen	decreases chemical synthesis, affects binding, increases reaction, increases expression, affects cotreatment (+2 more)	5
8-Bromo Cyclic Adenosine Monophosphate	increases activity, increases expression	5
alpha-naphthoflavone	decreases expression, decreases response to substance, affects binding, decreases activity, decreases reaction (+1 more)	4
mono-(2-ethylhexyl)phthalate	decreases reaction, increases expression, decreases activity, decreases expression	4
sodium arsenite	decreases reaction, increases activity, increases abundance, affects cotreatment, decreases expression (+2 more)	4

ChEMBL screening assays

728 unique, capped per target: 698 binding, 17 admet, 13 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1002232	Binding	Inhibition of human placental CYP19 at 500 nM	Overcoming undesirable CYP1A2 inhibition of pyridylnaphthalene-type aldosterone synthase inhibitors: influence of heteroaryl derivatization on potency and selectivity. — J Med Chem
CHEMBL1669904	ADMET	Inhibition of human CYP19 at 10 uM	Human cytochrome P450 liability studies of trans-dihydronarciclasine: a readily available, potent, and selective cancer cell growth inhibitor. — J Nat Prod
CHEMBL647446	Functional	Effective dose for inhibition of extragonadal estrogen production in baboons	Is there a case for P-450 inhibitors in cancer treatment? — J Med Chem

Cellosaurus cell lines

21 cell lines: 18 cancer cell line, 3 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_9580	MCF-7aro	Cancer cell line	Female
CVCL_9581	MCF-7aro/ERE	Cancer cell line	Female
CVCL_9582	T-47Daro	Cancer cell line	Female
CVCL_C8MT	MCF-7 AC1	Cancer cell line	Female
CVCL_C8NC	MCF-7 AC1-ExR	Cancer cell line	Female
CVCL_E1V0	HAP1 CYP19A1 (-) 2	Cancer cell line	Male
CVCL_E1V1	HAP1 CYP19A1 (-) 3	Cancer cell line	Male
CVCL_E1V2	HAP1 CYP19A1 (-) 4	Cancer cell line	Male
CVCL_E1V3	HAP1 CYP19A1 (-) 5	Cancer cell line	Male
CVCL_E1V4	HAP1 CYP19A1 (-) 6	Cancer cell line	Male

Clinical trials (associated diseases)

75 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists