Protein / target
Steroid 17-alpha-hydroxylase/17,20 lyase
Protein at a glance
Biological role
Steroid 17-alpha-monooxygenase activity
Primary system
Nervous system
Strongest disease association
congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
3 approved · 3 in clinical development
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 involved in corticoid and androgen biosynthesis (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:9452426). Catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol (Probable) (PubMed:25301938, PubMed:9452426). Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:36640554, PubMed:9452426). Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA (PubMed:36640554). Also 16-alpha hydroxylates androgens, relevant for estriol synthesis (PubMed:25301938, PubMed:27339894). 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:22266943, PubMed:25301938, PubMed:27339894, PubMed:9452426)
Subcellular location
Domains and Gene Ontology detail (17)Hide
Gene Ontology
- Caxon
- Cendoplasmic reticulum
- Cendoplasmic reticulum membrane
- Cneuronal cell body
- Fheme binding
- Firon ion binding
- Flyase activity
- Foxygen binding
- Fsteroid 17-alpha-monooxygenase activity
- Pandrogen biosynthetic process
- Pcortisol biosynthetic process
- Pglucocorticoid biosynthetic 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
- ·progesterone metabolic process
- ·steroid 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 17A1 inhibitor
Appears in clinical studies involving prostate cancer, prostate carcinoma, prostate neoplasm, prostate cancer
Cytochrome P450 17A1 inhibitor
Appears in clinical studies involving prostate cancer, prostate neoplasm, neoplasm, 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.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 570 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 cancer · prostate cancer · triple-negative breast carcinoma
Cushing syndrome · adrenal gland hyperfunction · adrenal gland disorder
prostate cancer · breast cancer · ovarian granulosa cell tumor
prostate cancer · pancreatic adenocarcinoma
prostate cancer · prostate neoplasm · neoplasm
prostate cancer · prostate carcinoma · prostate neoplasm
Tractability
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 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Label change
Label change: ABIRATERONE ACETATE (ANDA208371)
- New publicationNiraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial.
- New publicationAR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients.
- New publicationLuteinizing hormone-releasing hormone receptor agonists and antagonists in prostate cancer: effects on long-term survival and combined therapy with next-generation hormonal agents.
- New publicationCirculating Tumor DNA Assessment for Treatment Monitoring Adds Value to PSA in Metastatic Castration-Resistant Prostate Cancer.
- New publicationRucaparib or Physician's Choice in Metastatic Prostate Cancer.
- Regulatory approval
Approval: Abiraterone Mylan (EMA)
- Regulatory approval
Approval: Abiraterone Krka (EMA)
- Regulatory approval
Approval: Abiraterone Accord (EMA)
- New publicationOlaparib for Metastatic Castration-Resistant Prostate Cancer.
- New publicationCabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer.
- New publicationGenomic correlates of clinical outcome in advanced prostate cancer.
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.