Protein / target
Aromatase
Protein at a glance
Biological role
Estrogen 2-hydroxylase activity
Primary system
Endocrine & metabolic
Strongest disease association
aromatase deficiency
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
6 approved
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from 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 (PubMed:27702664, PubMed:2848247). 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 (PubMed:20385561). 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 (PubMed:22773874). Also displays 2-hydroxylase activity toward estrone (PubMed:22773874). 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) (PubMed:20385561, PubMed:22773874)
Subcellular location
Domains and Gene Ontology detail (19)Hide
Gene Ontology
- Cendoplasmic reticulum
- Cendoplasmic reticulum membrane
- Cmembrane
- Faromatase activity
- Felectron transfer activity
- Festrogen 2-hydroxylase activity
- Fheme binding
- Firon ion binding
- Foxidoreductase 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
- Foxygen binding
- Fsteroid hydroxylase activity
- Pandrogen catabolic process
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Metabolic enzyme activity
- ·oxidoreductase activity, acting on paired donors, with incorporation or reduction of mol…
- ·sterol metabolic process
View underlying pathways (3)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Cytochrome P450 19A1 inhibitor
Appears in clinical studies involving breast carcinoma, breast cancer, neoplasm, hypogonadotropic hypogonadism
Cytochrome P450 19A1 inhibitor
Appears in clinical studies involving breast carcinoma, breast cancer, neoplasm, ductal breast carcinoma in situ
Cytochrome P450 19A1 inhibitor
Appears in clinical studies involving breast carcinoma, breast cancer, neoplasm, breast cancer
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Show all associationsHide all associations
Open Targets ranks 1,854 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 6 total
breast carcinoma · breast cancer · neoplasm
breast carcinoma · breast cancer · neoplasm
breast cancer · congenital adrenal hyperplasia · precocious puberty
breast cancer
breast carcinoma · breast cancer · neoplasm
neoplasm · breast cancer · prostate cancer
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 3 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- New publicationChronic Aromatase Inhibition Attenuates Synaptic Plasticity in Ovariectomized Mice.
- New publicationAbemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3.
- New publicationEfficacy, safety, and biomarker analysis of nivolumab in combination with abemaciclib plus endocrine therapy in patients with HR-positive HER2-negative metastatic breast cancer: a phase II study (WJOG11418B NEWFLAME trial).
- New publicationClinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases.
- New publicationA randomized phase II trial of ridaforolimus, dalotuzumab, and exemestane compared with ridaforolimus and exemestane in patients with advanced breast cancer.
- New publicationA Phase II Clinical Trial of an Aromatase Inhibitor for Postmenopausal Women with Lymphangioleiomyomatosis.
- New publicationAnastrozole in Pulmonary Arterial Hypertension. A Randomized, Double-Blind, Placebo-controlled Trial.
- New publicationPalbociclib and Letrozole in Advanced Breast Cancer.
- New publicationRibociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.
- New publicationExtending Aromatase-Inhibitor Adjuvant Therapy to 10 Years.
- New publicationLetrozole versus clomiphene for infertility in the polycystic ovary syndrome.
- New publicationExemestane for breast-cancer prevention in postmenopausal women.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.