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Protein / target

3-oxo-5-alpha-steroid 4-dehydrogenase 2

Encoded bySRD5A2P31213Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

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

Strongest disease association

46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency

Via encoding gene SRD5A2 · Genetic evidence · score 0.94

Therapeutic position

Established drug target

Small molecules

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 overview

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.

View complete UniProt function annotation

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:10898110, PubMed:23685396). Converts testosterone into 5-alpha-dihydrotestosterone (DHT), the most active androgen in the prostate, as it is the preferred ligand for androgen receptor (AR) transactivation, making this reaction a key step in male sexual differentiation during development (PubMed:10898110, PubMed:23685396). Besides testosterone, it can also act on other steroids, including progesterone, producing metabolites with diverse roles (PubMed:10898110). Hence, it plays a central role in sexual differentiation and androgen physiology (PubMed:10898110)

Subcellular location

Microsome membraneEndoplasmic reticulum membrane
Domains and Gene Ontology detail (28)

Gene Ontology

  • Ccell body fiber
  • Cendoplasmic reticulum membrane
  • Cneuronal cell body
  • F3-oxo-5-alpha-steroid 4-dehydrogenase (NADP+) activity
  • F3-oxo-5-alpha-steroid 4-dehydrogenase activity
  • Famide binding
  • Ftestosterone dehydrogenase (NADP+) activity
  • Pandrogen biosynthetic process
  • Pandrogen metabolic process
  • Pbone development
  • Pcell differentiation
  • Pcell-cell signaling

254 aa · 28 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
  • ·testosterone dehydrogenase (NADP+) activity
  • ·androgen 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.

CYP17A1HSD17B3HSD3B2AKR1C3AKR1C2HSD3B1CYP19A1AKR1C4HSD17B2AKR1D1SRD5A2

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.

Approved medicines with mapped indications

2 medicines · 3 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Alopecia1 medicine
Prostatic Neoplasms1 medicine
Neoplasms1 medicine

3 medicines meet Open Targets' target-level approved-medicine definition; the 2 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

2

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

finasteride
Narrow target profileApprovedInhibitor

Steroid 5-alpha-reductase 2 inhibitor

Indicated for Alopecia, Prostatic Neoplasms

Direct interaction with this protein · Only this protein recorded as a target

abiraterone
ApprovedInhibitor

Steroid 5-alpha-reductase inhibitor

Indicated for Neoplasms

Acts on a complex — shared with SRD5A1, SRD5A3 · 1 of 5 recorded protein targets

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

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene SRD5A2

Gene-level evidence surfaced through the gene SRD5A2that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency
0.97Well supported

Genetic evidence dominant · Open Targets 0.84

Alopecia
0.92Well supported

Clinical evidence dominant · Open Targets 0.70

Benign prostatic hyperplasia
0.82Well supported

Clinical evidence dominant · Open Targets 0.63

Prostate carcinoma
0.80Well supported

Clinical evidence dominant · Open Targets 0.62

Prostatic Neoplasms
0.76Well supported

Clinical evidence dominant · Open Targets 0.57

View evidence synthesis (5)
46,XY disorder of sex development due to 5-alpha-reductase 2 deficiencyWell supported
0.97
agreement 0.871.00
Genetic63%Somatic mutation25%Animal model11%Literature1%Genetic literaturedup

Open Targets aggregate 0.84 · 4 independent evidence families · 1 not counted as duplicate

AlopeciaWell supported
0.92
agreement 0.811.00
Clinical51%Genetic49%Literature1%

Open Targets aggregate 0.70 · 3 independent evidence families

Benign prostatic hyperplasiaWell supported
0.82
agreement 0.690.94
Clinical71%Animal model19%Literature11%

Open Targets aggregate 0.63 · 3 independent evidence families

Prostate carcinomaWell supported
0.80
agreement 0.670.93
Clinical75%Animal model20%Literature5%

Open Targets aggregate 0.62 · 3 independent evidence families

Prostatic NeoplasmsWell supported
0.76
agreement 0.630.88
Clinical74%Animal model22%Literature5%

Open Targets aggregate 0.57 · 3 independent evidence families

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 per-type scores above show the calculation.

Show all associations
46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency0.84
Alopecia0.70
Benign prostatic hyperplasia0.63
Prostate carcinoma0.62
Prostatic Neoplasms0.57
Hypogonadism0.41
Prostate neoplasm0.39

Drug development

3 compounds recorded · 3 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (3)
DUTASTERIDEApproval
ABIRATERONEApproval
FINASTERIDEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot sigp or tmhmm) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (6)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Label change2026-07-02

    Label change: FINASTERIDE (ANDA076511)

    fda · regulatory · fda · via finasteride

  2. Label change2026-07-02

    Label change: FINASTERIDE (ANDA090121)

    fda · regulatory · fda · via finasteride

  3. Label change2026-07-01

    Label change: FINASTERIDE (ANDA076437)

    fda · regulatory · fda · via finasteride

  4. Label change2026-07-01

    Label change: FINASTERIDE (ANDA078341)

    fda · regulatory · fda · via finasteride

  5. Label change2026-01-26

    Label change: FINASTERIDE (ANDA076511)

    fda · regulatory · fda · via finasteride

  6. 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

  7. 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

  8. 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

  9. Safety communication2024-04-29

    Drug Safety Update: Finasteride: reminder of the risk psychiatric side effects and of sexual side effects (which may persist after discontinuation of treatment)

    mhra · safety · mhra · via finasteride

  10. 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

  11. Safety communication2017-05-24

    Drug Safety Update: Finasteride: rare reports of depression and suicidal thoughts

    mhra · safety · mhra · via finasteride

  12. Safety communication2014-12-11

    Drug Safety Update: Finasteride: potential risk of male breast cancer

    mhra · safety · mhra · via finasteride

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.