Protein / target

3-oxo-5-alpha-steroid 4-dehydrogenase 1

SRD5A1P18405Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
2
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

3-oxo-5-alpha-steroid 4-dehydrogenase (NADP+) activity

Primary system

Endocrine & metabolic

Strongest disease association

hypertrophic cardiomyopathy

Genetic evidence · score 0.50

Therapeutic maturity

Clinically validated target

2 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

2 approved

30 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

Catalyzes the irreversible stereospecific reduction of the delta 4,5 bond (double bond between carbons 4 and 5) of various 3-oxo steroids (3-keto steroids) producing their 5alpha dihydro-3-oxo forms (PubMed:2339109, PubMed:23685396). Converts testosterone into 5-alpha-dihydrotestosterone (DHT), a more potent androgen as it is the preferred ligand for androgen receptor (AR) transactivation, making this reaction a key step in male sexual differentiation during development (PubMed:2339109, PubMed:23685396). Besides testosterone, it can also act on other steroids, including progesterone, androstenedione, and corticoids, producing metabolites with diverse roles (PubMed:2339109). Hence, it plays a central role in sexual differentiation and androgen physiology (PubMed:2339109)

Subcellular location

Microsome membraneEndoplasmic reticulum membrane
Domains and Gene Ontology detail (43)

Gene Ontology

  • Ccell body fiber
  • Cendoplasmic reticulum membrane
  • Cneuronal cell body
  • Cperinuclear region of cytoplasm
  • F3-oxo-5-alpha-steroid 4-dehydrogenase (NADP+) activity
  • F3-oxo-5-alpha-steroid 4-dehydrogenase activity
  • Famide binding
  • Felectron transfer activity
  • FNADPH binding
  • Pandrogen biosynthetic process
  • Pandrogen catabolic process
  • Pbone development

259 aa · 29 kDa

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Metabolic enzyme activityGO
View supporting evidence

Metabolic enzyme activity

  • ·3-oxo-5-alpha-steroid 4-dehydrogenase (NADP+) activity
  • ·3-oxo-5-alpha-steroid 4-dehydrogenase activity
  • ·diterpenoid metabolic process
  • ·progesterone metabolic process
View underlying pathways (1)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

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.

SRD5A3CYP17A1AKR1D1AKR1C3HSD3B2HSD17B3AKR1C2HSD17B2HSD17B6AKR1C1SRD5A1

10 strongest partners — larger node and heavier line mean higher confidence

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

1

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.

abiraterone
ApprovedInhibitor

Steroid 5-alpha-reductase inhibitor

Appears in clinical studies involving prostate cancer, prostate neoplasm, neoplasm, cancer

Acts on a complex — shared with SRD5A2, SRD5A3 · 1 of 5 recorded protein targets

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

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.

hypertrophic cardiomyopathy0.50

Genetic · overall 0.30

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

benign prostatic hyperplasia0.97

Clinical · overall 0.59

prostate cancer0.91

Clinical · overall 0.57

prostate carcinoma0.89

Clinical · overall 0.56

androgenetic alopecia0.83

Clinical · overall 0.51

neoplasm0.62

Clinical · overall 0.38

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

prostate neoplasm0.37

Clinical

alopecia0.37

Clinical

hypogonadism0.34

Clinical

chronic prostatitis0.30

Clinical

Show all associations
benign prostatic hyperplasia0.59
prostate cancer0.57
prostate carcinoma0.56
androgenetic alopecia0.51
neoplasm0.38
prostate neoplasm0.37
alopecia0.37
hypogonadism0.34
chronic prostatitis0.30
hypertrophic cardiomyopathy0.30

Open Targets ranks 164 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 · 2 total

DUTASTERIDEApproval

androgenetic alopecia · prostate carcinoma · benign prostatic hyperplasia

ABIRATERONEApproval

prostate cancer · prostate neoplasm · neoplasm

Tractability

SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule Binder

Clinical trials

30

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)

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

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.

benign prostatic hyperplasiaModerately supported
0.73
agreement 0.580.89
Clinical96%Literature4%

Open Targets aggregate 0.59 · 2 independent evidence families

prostate cancerModerately supported
0.70
agreement 0.550.86
Clinical91%Literature9%

Open Targets aggregate 0.57 · 2 independent evidence families

prostate carcinomaModerately supported
0.69
agreement 0.540.85
Clinical91%Literature10%

Open Targets aggregate 0.56 · 2 independent evidence families

androgenetic alopeciaModerately supported
0.63
agreement 0.470.78
Clinical98%Literature2%

Open Targets aggregate 0.51 · 2 independent evidence families

hypertrophic cardiomyopathyLimited support
0.50
agreement 0.380.62
Genetic100%

Open Targets aggregate 0.30 · 1 independent evidence family

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

12

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2024-12-11
    AR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients.

    Nature communications · 2024 · 11 citations · Europe PMC · via abiraterone

  2. New publication2024-12-01
    Luteinizing hormone-releasing hormone receptor agonists and antagonists in prostate cancer: effects on long-term survival and combined therapy with next-generation hormonal agents.

    Cancer biology & medicine · 2024 · 9 citations · Europe PMC · via abiraterone

  3. New publication2024-09-01
    Circulating Tumor DNA Assessment for Treatment Monitoring Adds Value to PSA in Metastatic Castration-Resistant Prostate Cancer.

    Clinical cancer research : an official journal of the American Association for Cancer Research · 2024 · 19 citations · Europe PMC · via abiraterone

  4. New publication2023-02-16
    Rucaparib or Physician's Choice in Metastatic Prostate Cancer.

    The New England journal of medicine · 2023 · 332 citations · Europe PMC · via abiraterone

  5. Regulatory approval2021-08-20

    Approval: Abiraterone Mylan (EMA)

    ema · regulatory · ema · via abiraterone

  6. Regulatory approval2021-06-24

    Approval: Abiraterone Krka (EMA)

    ema · regulatory · ema · via abiraterone

  7. Regulatory approval2021-04-26

    Approval: Abiraterone Accord (EMA)

    ema · regulatory · ema · via abiraterone

  8. New publication2020-04-28
    Olaparib for Metastatic Castration-Resistant Prostate Cancer.

    The New England journal of medicine · 2020 · 1,688 citations · Europe PMC · via abiraterone

  9. New publication2019-09-30
    Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer.

    The New England journal of medicine · 2019 · 439 citations · Europe PMC · via abiraterone

  10. New publication2019-05-06
    Genomic correlates of clinical outcome in advanced prostate cancer.

    Proceedings of the National Academy of Sciences of the United States of America · 2019 · 1,163 citations · Europe PMC · via abiraterone

  11. New publication2019-02-06
    Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial.

    The Lancet. Oncology · 2019 · 288 citations · Europe PMC · via abiraterone

  12. Accelerated approval granted2011-09-05

    Accelerated approval: Zytiga (EMA)

    ema · regulatory · ema · via abiraterone

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.