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Protein / target

Mineralocorticoid receptor

Encoded byNR3C2P08235Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
13
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Sequence-specific double-stranded DNA binding

Strongest disease association

Autosomal dominant pseudohypoaldosteronism type 1

Via encoding gene NR3C2 · Genetic evidence · score 0.92

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

Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol.

View complete UniProt function annotation

Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels

Subcellular location

CytoplasmNucleusEndoplasmic reticulum membrane
Domains and Gene Ontology detail (21)

Domains & features

NR LBD

Gene Ontology

  • Cchromatin
  • Ccytosol
  • Cendoplasmic reticulum membrane
  • Cnucleoplasm
  • Cnucleus
  • Creceptor complex
  • FDNA-binding transcription factor activity
  • FDNA-binding transcription factor activity, RNA polymerase II-specific
  • Festrogen response element binding
  • Fnuclear receptor activity
  • Fnuclear steroid receptor activity
  • Fsequence-specific double-stranded DNA binding

984 aa · 107 kDa · 4 isoforms

Biological roles

Reactome v97

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

Nuclear receptor signallingGO · ReactomeTranscriptional regulationGO · Reactome
View supporting evidence

Nuclear receptor signalling

  • ·nuclear receptor activity
  • ·nuclear receptor-mediated steroid hormone signaling pathway
  • ·HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
  • ·Nuclear Receptor transcription pathway

Transcriptional regulation

  • ·DNA-binding transcription factor activity
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific
  • ·DNA-templated transcription
  • ·regulation of transcription by RNA polymerase II
View underlying pathways (3)

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.

NCOA1AGTFKBP4RENNR3C1HSD11B2ACEHSP90A…PTGES3HSP90A…NR3C2

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

4 medicines · 13 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.

Diabetes Mellitus, Type 21 medicine
Edema1 medicine
Essential Hypertension1 medicine
Fibrosis1 medicine
Heart Failure1 medicine
Hyperaldosteronism1 medicine
Hypertension1 medicine
Liver Cirrhosis1 medicine
Muscular Dystrophy, Duchenne1 medicine
Myocardial Infarction1 medicine
Nephrotic Syndrome1 medicine
Renal Insufficiency, Chronic1 medicine
Cardiovascular Diseases3 medicines

13 medicines meet Open Targets' target-level approved-medicine definition; the 4 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

4

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.

Spironolactone
Narrow target profileApprovedAntagonist

Mineralocorticoid receptor antagonist

Indicated for Edema, Essential Hypertension, Fibrosis, Heart Failure

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

finerenone
Narrow target profileApprovedAntagonist

Mineralocorticoid receptor antagonist

Indicated for Diabetes Mellitus, Type 2, Renal Insufficiency, Chronic, Cardiovascular Diseases

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

vamorolone
Narrow target profileApprovedAntagonist

Mineralocorticoid receptor antagonist

Indicated for Muscular Dystrophy, Duchenne

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

Nimodipine
ApprovedAntagonist

Mineralocorticoid receptor antagonist

Indicated for Cardiovascular Diseases

Direct interaction with this protein · 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 NR3C2

Gene-level evidence surfaced through the gene NR3C2 that 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.

Hypertension
0.96Well supported

Genetic evidence dominant · Open Targets 0.74

Autosomal dominant pseudohypoaldosteronism type 1
0.93Well supported

Genetic evidence dominant · Open Targets 0.78

Renal pseudohypoaldosteronism type 1
0.88Well supported

Genetic evidence dominant · Open Targets 0.73

Pseudohyperaldosteronism type 2
0.79Well supported

Genetic evidence dominant · Open Targets 0.69

Nephrotic Syndrome
0.77Well supported

Clinical evidence dominant · Open Targets 0.58

View evidence synthesis (5)
HypertensionWell supported
0.96
agreement 0.851.00
Genetic51%Clinical45%Literature5%

Open Targets aggregate 0.74 · 3 independent evidence families

Autosomal dominant pseudohypoaldosteronism type 1Well supported
0.93
agreement 0.811.00
Genetic87%Animal model12%Literature2%Genetic literaturedup

Open Targets aggregate 0.78 · 3 independent evidence families · 1 not counted as duplicate

Renal pseudohypoaldosteronism type 1Well supported
0.88
agreement 0.761.00
Genetic85%Animal model13%Literature2%Genetic literaturedup

Open Targets aggregate 0.73 · 3 independent evidence families · 1 not counted as duplicate

Pseudohyperaldosteronism type 2Well supported
0.79
agreement 0.670.91
Genetic100%Genetic literaturedup

Open Targets aggregate 0.69 · 1 independent evidence family · 1 not counted as duplicate

Nephrotic SyndromeWell supported
0.77
agreement 0.640.90
Clinical74%Animal model25%Literature1%

Open Targets aggregate 0.58 · 3 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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
Autosomal dominant pseudohypoaldosteronism type 10.78
Hypertension0.74
Renal pseudohypoaldosteronism type 10.73
Pseudohyperaldosteronism type 20.69
Heart Failure0.61
Myocardial Infarction0.60
Kidney Failure, Chronic0.60
Diabetes Mellitus, Type 20.59
Nephrotic Syndrome0.58

Drug development

17 compounds recorded · 13 approved · 4 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 4 drugs that target this protein in Forefront's canonical graph (4 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
LY2623091Phase 2
XL550Approval
MT-3995Phase 2
FINERENONEApproval
DESOXYCORTICOSTERONE PIVALATEApproval
DESOXYCORTICOSTERONE ACETATEApproval
FLUDROCORTISONE ACETATEApproval
FELODIPINEApproval
DROSPIRENONEApproval
CANRENONEApproval

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 loc med conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

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

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketSM · Druggable FamilyAB · UniProt loc med confPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of steroid hormone biosynthetic processToxCastregulation of transcription factor activityToxCastregulation of steroid biosynthetic processToxCast

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

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)

NOT_YET_RECRUITING · via finerenone · NCT07155694

RECRUITING · via Spironolactone · NCT05092984

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 3 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 change2026-08-13

    Label change: SPIRONOLACTONE (ANDA040750)

    fda · regulatory · fda · via Spironolactone

  2. Label change2026-08-11

    Label change: SPIRONOLACTONE (ANDA089424)

    fda · regulatory · fda · via Spironolactone

  3. Label change2026-08-11

    Label change: SPIRONOLACTONE (ANDA091426)

    fda · regulatory · fda · via Spironolactone

  4. Label change2026-08-11

    Label change: SPIRONOLACTONE (ANDA202187)

    fda · regulatory · fda · via Spironolactone

  5. Label change2026-08-11

    Label change: SPIRONOLACTONE (ANDA205936)

    fda · regulatory · fda · via Spironolactone

  6. Label change2025-06-17

    Label change: SPIRONOLACTONE (ANDA089424)

    fda · regulatory · fda · via Spironolactone

  7. New publication2024-11-15
    Updated evidence on cardiovascular and renal effects of GLP-1 receptor agonists and combination therapy with SGLT2 inhibitors and finerenone: a narrative review and perspectives.

    Cardiovascular diabetology · 2024 · 23 citations · Europe PMC · via finerenone

  8. New publication2024-01-30
    Guidelines of care for the management of acne vulgaris.

    Journal of the American Academy of Dermatology · 2024 · 236 citations · Europe PMC · via Spironolactone

  9. Regulatory approval2023-12-14

    Approval: Agamree (EMA)

    ema · regulatory · ema · via vamorolone

  10. Regulatory approval2023-05-26

    Approval: Qaialdo (EMA)

    ema · regulatory · ema · via Spironolactone

  11. New publication2022-02-01
    Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis.

    European heart journal · 2022 · 719 citations · Europe PMC · via finerenone

  12. New publication1999-09-01
    The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.

    The New England journal of medicine · 1999 · 5,811 citations · Europe PMC · via Spironolactone

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.

Related literature

1

Papers indexed under “Receptors, Mineralocorticoid” — a subject heading that covers this protein without being specific to it. Shown as context; not counted as this protein's own research activity.

Europe PMC literature, reached through a MeSH descriptor linked to this protein.