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Protein / target

Glucocorticoid receptor

Encoded byNR3C1P04150Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
55
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

Glucocorticoid resistance

Via encoding gene NR3C1 · 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 glucocorticoids (GC).

View complete UniProt function annotation

Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity)

Subcellular location

CytoplasmNucleusMitochondrionCytoplasm, cytoskeleton, spindleCytoplasm, cytoskeleton, microtubule organizing center, centrosomeChromosomeNucleus, nucleoplasm
Domains and Gene Ontology detail (56)

Domains & features

NR LBD

Gene Ontology

  • Ccentrosome
  • Cchromatin
  • Ccytoplasm
  • Ccytosol
  • Cmembrane
  • Cmitochondrial matrix
  • Cmitochondrion
  • Cnuclear speck
  • Cnucleoplasm
  • Cnucleus
  • Cprotein-containing complex
  • Cspindle

777 aa · 86 kDa · 16 isoforms

Biological roles

Reactome v97

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

Nuclear receptor signallingGO · ReactomeExcitatory neurotransmissionGOTranscriptional regulationUniProt · GO · ReactomeImmune signallingUniProt · GO
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

Excitatory neurotransmission

  • ·synaptic transmission, glutamatergic

Transcriptional regulation

  • ·Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of…
  • ·DNA-binding transcription activator activity, RNA polymerase II-specific
  • ·DNA-binding transcription factor activity
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific

Immune signalling

  • ·Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of…
  • ·neuroinflammatory response
View underlying pathways (8)

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.

FKBP5HSP90A…NCOA2HSP90A…PTGES3NCOA1FKBP4NCOR1STIP1HSPA4NR3C1

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

11 medicines · 60 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.

Adrenal Hyperplasia, Congenital4 medicines
Dermatitis, Seborrheic4 medicines
Anemia, Aplastic3 medicines
Arthritis, Gouty3 medicines
Chorioretinitis3 medicines
Dermatitis Herpetiformis3 medicines
Dermatitis, Contact3 medicines
Endocrine System Diseases3 medicines
Hypercalcemia3 medicines
Lung Diseases, Obstructive3 medicines
Lupus Erythematosus, Systemic3 medicines
Mycosis Fungoides3 medicines
Nephrotic Syndrome3 medicines
Optic Neuritis3 medicines
Pulmonary Disease, Chronic Obstructive3 medicines
Spondylitis, Ankylosing3 medicines
Thrombocytopenia3 medicines
Tuberculosis, Meningeal3 medicines
Tuberculosis, Pulmonary3 medicines
Acne Vulgaris2 medicines
Dermatitis2 medicines
Pemphigus2 medicines
Purpura, Thrombocytopenic, Idiopathic2 medicines
Rhinitis, Allergic2 medicines
Adrenal Insufficiency1 medicine
Anemia1 medicine
Arthritis1 medicine
Brain Neoplasms1 medicine
Cushing's Syndrome1 medicine
Diabetic Retinopathy1 medicine
Exanthema1 medicine
Glomerulonephritis, IGA1 medicine
Infections1 medicine
Macular Edema1 medicine
Muscular Dystrophy, Duchenne1 medicine
Nasal Polyps1 medicine
Pruritus1 medicine
Uveitis1 medicine
Broader indication categories (1)

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

55 medicines meet Open Targets' target-level approved-medicine definition; the 11 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

12

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.

Hydrocortisone
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Indicated for Adrenal Hyperplasia, Congenital, Adrenal Insufficiency, Arthritis, Juvenile, Arthritis, Psoriatic

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

Dexamethasone
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Indicated for Acne Vulgaris, Adrenal Hyperplasia, Congenital, Anemia, Aplastic, Arthritis, Gouty

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

Prednisolone
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Indicated for Adrenal Hyperplasia, Congenital, Anemia, Aplastic, Arthritis, Gouty, Arthritis, Juvenile

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

Prednisone
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Indicated for Adrenal Hyperplasia, Congenital, Anemia, Anemia, Aplastic, Arthritis

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

Cyproterone Acetate
Narrow target profilePhase 3Antagonist

Glucocorticoid receptor antagonist

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

Budesonide
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Indicated for Asthma, Colitis, Ulcerative, Crohn's Disease, Glomerulonephritis, IGA

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

View all 12 targeting drugs
Methylprednisolone
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Indicated for Acne Vulgaris, Arthritis, Juvenile, Arthritis, Psoriatic, Arthritis, Rheumatoid

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

Mifepristone
Narrow target profileApprovedAntagonist

Glucocorticoid receptor antagonist

Indicated for Cushing's Syndrome

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

fluocinonide
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Indicated for Skin Diseases

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

fluticasone propionate
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Indicated for Asthma, Dermatitis, Atopic, Lung Diseases, Obstructive, Nasal Polyps

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

fluticasone furoate
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Indicated for Asthma, Lung Diseases, Obstructive, Pulmonary Disease, Chronic Obstructive

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

vamorolone
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Indicated for Muscular Dystrophy, Duchenne

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

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 NR3C1

Gene-level evidence surfaced through the gene NR3C1 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.

Glucocorticoid resistance
0.94Well supported

Genetic evidence dominant · Open Targets 0.81

Pulmonary Disease, Chronic Obstructive
0.90Well supported

Clinical evidence dominant · Open Targets 0.70

Multiple Sclerosis
0.81Well supported

Clinical evidence dominant · Open Targets 0.69

Sarcoidosis
0.81Well supported

Clinical evidence dominant · Open Targets 0.62

Arthritis, Rheumatoid
0.80Well supported

Clinical evidence dominant · Open Targets 0.63

View evidence synthesis (5)
Glucocorticoid resistanceWell supported
0.94
agreement 0.821.00
Genetic79%Animal model17%Literature4%Genetic literaturedup

Open Targets aggregate 0.81 · 3 independent evidence families · 1 not counted as duplicate

Pulmonary Disease, Chronic ObstructiveWell supported
0.90
agreement 0.801.00
Clinical52%Genetic39%Literature9%

Open Targets aggregate 0.70 · 3 independent evidence families

Multiple SclerosisWell supported
0.81
agreement 0.680.94
Clinical74%Pathway20%Literature7%

Open Targets aggregate 0.69 · 3 independent evidence families

SarcoidosisWell supported
0.81
agreement 0.680.93
Clinical75%Animal model22%Literature3%

Open Targets aggregate 0.62 · 3 independent evidence families

Arthritis, RheumatoidWell supported
0.80
agreement 0.690.91
Clinical77%Genetic15%Literature8%

Open Targets aggregate 0.63 · 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
Glucocorticoid resistance0.81
Pulmonary Disease, Chronic Obstructive0.70
Multiple Sclerosis0.69
Arthritis, Rheumatoid0.63
Asthma0.63
Multiple Myeloma0.62
Sarcoidosis0.62
Infections0.62
Purpura, Thrombocytopenic, Idiopathic0.62
Osteoarthritis0.62

Drug development

71 compounds recorded · 55 approved · 14 in clinical development · 2 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 12 drugs that target this protein in Forefront's canonical graph (11 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
TRIAMCINOLONEApproval
METHYLPREDNISOLONE HEMISUCCINATEPhase 2 3
TRIAMCINOLONE DIACETATEUnknown
HYDROCORTISONE SODIUM SUCCINATEApproval
METHYLPREDNISOLONE ACETATEApproval
HYDROCORTISONE PROBUTATEApproval
FLUTICASONE FUROATEApproval
FOSDAGROCORATPhase 2
DESOXIMETASONEApproval
BUDESONIDEApproval

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.

Protein degradersEmerging

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

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (10)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of transcription factor activityToxCastdecreased memoryLynch et al. (2017)immunosuppressionBowes et al. (2012)muscle wastingBowes et al. (2012)Decreased sperm quantity / quality in the adult, Decreased fertilityAOP-Wikidecreased blood potassiumLynch et al. (2017)decreased wound repairLynch et al. (2017)receptor bindingToxCastincreased body weightBowes et al. (2012)glaucomaBowes et al. (2012)increased blood glucoseLynch et al. (2017)increased urinary sodium excretionLynch et al. (2017)

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)

ACTIVE_NOT_RECRUITING · via Dexamethasone · NCT03020030

ACTIVE_NOT_RECRUITING · via Dexamethasone · NCT05192889

ACTIVE_NOT_RECRUITING · via Prednisone · NCT03943901

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 7 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. Trial results posted2026-09-15

    Open Label, Phase 2, Single-Arm Study of Selinexor, Daratumumab, Carfilzomib and Dexamethasone for High-Risk, Relapsed and Relapsed/Refractory Multiple Myeloma Patients Who Have Received 1 - 3 Prior Lines of Therapy

    Results posted · ClinicalTrials.gov · via Dexamethasone

  2. Regulatory approval2026-08-18

    Approval: FLUTICASONE PROPIONATE (ANDA219232)

    fda · regulatory · fda · via fluticasone propionate

  3. Trial results posted2026-08-11

    A Randomized Phase II Pilot of Tailored Prednisone Reduction Versus Usual Care for the Treatment of Hyperglycemia During R-CHOP Chemotherapy

    Results posted · ClinicalTrials.gov · via Prednisone

  4. Trial results posted2026-07-28

    Phase 2 Study With Minimal Residual Disease (MRD) Driven Adaptive Strategy in Treatment for Newly Diagnosed Multiple Myeloma (MM) With Upfront Daratumumab-based Therapy

    Results posted · ClinicalTrials.gov · via Dexamethasone

  5. Regulatory approval2026-07-27

    Approval: FLUTICASONE PROPIONATE AND SALMETEROL (ANDA213087)

    fda · regulatory · fda · via fluticasone propionate

  6. Trial results posted2026-07-24

    A Phase IIIB Multicenter, Randomized, Double-blind, Controlled Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis

    Results posted · ClinicalTrials.gov · via Methylprednisolone

  7. Regulatory approval2026-07-16

    Approval: HYDROCORTISONE (ANDA218298)

    fda · regulatory · fda · via Hydrocortisone

  8. Regulatory approval2026-06-26

    Approval: PREDNISONE (ANDA218035)

    fda · regulatory · fda · via Prednisone

  9. Product recall2026-05-29

    Recall (Class II): BUDESONIDE

    fda · safety · fda · via Budesonide

  10. Product recall2026-03-25

    Recall (Class II): FLUOCINONIDE

    fda · safety · fda · via fluocinonide

  11. New publication2025-10-07
    Niraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial.

    Nature medicine · 2025 · 19 citations · Europe PMC · via Prednisone

  12. New publication2025-09-16
    The cortisol axis and psychiatric disorders: an updated review.

    Pharmacological reports : PR · 2025 · 8 citations · Europe PMC · via Hydrocortisone

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

6

Papers indexed under “Receptors, Glucocorticoid” — 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.