Protein / target

Glucocorticoid receptor

NR3C1P04150Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
55
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Sequence-specific double-stranded DNA binding

Primary system

Nervous system

Strongest disease association

glucocorticoid resistance

Genetic evidence · score 0.92

Therapeutic maturity

Clinically validated target

55 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

55 approved · 14 in clinical development

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

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.

Transcriptional regulationUniProt · GO · ReactomeNuclear receptor signallingGO · ReactomeImmune signallingUniProt · GOSynaptic signallingGOExcitatory neurotransmissionGOKinase signallingGO
View supporting evidence

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

Nuclear receptor signalling

  • ·DNA-binding transcription factor activity
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific
  • ·nuclear receptor activity
  • ·nuclear receptor-mediated steroid hormone signaling pathway

Immune signalling

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

Synaptic signalling

  • ·synapse
  • ·synaptic transmission, glutamatergic

Excitatory neurotransmission

  • ·synaptic transmission, glutamatergic

Kinase signalling

  • ·protein kinase binding
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.

Drugs targeting this protein

8

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.

Hydrocortisone
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Appears in clinical studies involving inflammation, otitis externa, skin disorder, osteoarthritis

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

Dexamethasone
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Appears in clinical studies involving infection, inflammation, Corneal scarring, cancer

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

Prednisolone
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Appears in clinical studies involving sarcoidosis, osteoarthritis, asthma, juvenile idiopathic arthritis

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

Prednisone
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Appears in clinical studies involving sarcoidosis, trichinosis, choroiditis, asthma

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

Cyproterone Acetate
Narrow target profilePhase 3Antagonist

Glucocorticoid receptor antagonist

Appears in clinical studies involving prostate cancer, Hot flashes, prostate adenocarcinoma, endometriosis

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

Budesonide
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Appears in clinical studies involving ulcerative colitis, Nasal congestion, seasonal allergic rhinitis, asthma

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

Methylprednisolone
Narrow target profileApprovedAgonist

Glucocorticoid receptor agonist

Appears in clinical studies involving osteoarthritis, inflammation, multiple sclerosis, asthma

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

Mifepristone
Narrow target profileApprovedAntagonist

Glucocorticoid receptor antagonist

Appears in clinical studies involving Cushing syndrome, psychotic disorder, major depressive disorder, Uterine leiomyoma

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

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.

glucocorticoid resistance0.92

Genetic · overall 0.81

chronic obstructive pulmonary disease0.56

Genetic · overall 0.70

rheumatoid arthritis0.14

Genetic · overall 0.63

osteoarthritis0.05

Genetic · overall 0.62

Highest-confidence therapeutic associations

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

asthma1.00

Clinical · overall 0.63

autoimmune thrombocytopenic purpura1.00

Clinical · overall 0.62

multiple sclerosis0.99

Clinical · overall 0.69

sarcoidosis0.99

Clinical · overall 0.62

plasma cell myeloma0.99

Clinical · overall 0.62

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

infection0.62

Clinical

Show all associations
glucocorticoid resistance0.81
chronic obstructive pulmonary disease0.70
multiple sclerosis0.69
rheumatoid arthritis0.63
asthma0.63
plasma cell myeloma0.62
sarcoidosis0.62
infection0.62
autoimmune thrombocytopenic purpura0.62
osteoarthritis0.62

Open Targets ranks 2,047 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 · 71 total

TRIAMCINOLONEApproval

skin disorder · hemorrhoid · allergic rhinitis

METHYLPREDNISOLONE HEMISUCCINATEPhase 2 3

optic nerve disorder · multiple sclerosis

TRIAMCINOLONE DIACETATEUnknown
HYDROCORTISONE SODIUM SUCCINATEApproval

asthma · acute lymphoblastic leukemia · acute leukemia of ambiguous lineage

METHYLPREDNISOLONE ACETATEApproval

dermatitis · anemia · asthma

HYDROCORTISONE PROBUTATEApproval

skin disorder

FLUTICASONE FUROATEApproval

allergic rhinitis · asthma · perennial allergic rhinitis

FOSDAGROCORATPhase 2

rheumatoid arthritis

DESOXIMETASONEApproval

skin disorder · psoriasis vulgaris · inflammation

BUDESONIDEApproval

ulcerative colitis · Nasal congestion · seasonal allergic rhinitis

Tractability

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

Safety liabilities

regulation of transcription factor activitydecreased memoryimmunosuppressionmuscle wastingDecreased sperm quantity / quality in the adult, Decreased fertilitydecreased blood potassiumdecreased wound repairreceptor bindingincreased body weightglaucomaincreased blood glucoseincreased urinary sodium excretion

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)

COMPLETED · via Hydrocortisone · NCT03748537

COMPLETED · via Dexamethasone · NCT01612702

COMPLETED · via Dexamethasone · NCT01390012

ClinicalTrials.gov via the drug-target graph.

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.

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.

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

chronic obstructive pulmonary diseaseWell 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

rheumatoid arthritisWell 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

60

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 8 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. Trial status changed2026-07-30

    64407564MMY3009: A Phase 3 Randomized Study Comparing Talquetamab in Combination With Pomalidomide (Tal-P), Talquetamab in Combination With Teclistamab (Tal-Tec), and Investigator's Choice of Either Elotuzumab, Pomalidomide, and Dexamethasone (EPd) or Pom

    Status changed to Active, not recruiting · ClinicalTrials.gov · via Dexamethasone

  2. Regulatory action2026-07-21
    Biotech industry leaders file brief backing FDA against ‘malicious’ mifepristone challenge

    Fierce Biotech · news · via Mifepristone

  3. Regulatory approval2026-07-16

    Approval: HYDROCORTISONE (ANDA218298)

    fda · regulatory · fda · via Hydrocortisone

  4. Regulatory approval2026-06-26

    Approval: PREDNISONE (ANDA218035)

    fda · regulatory · fda · via Prednisone

  5. Label change2026-06-25

    Label change: METHYLPREDNISOLONE (ANDA207549)

    fda · regulatory · fda · via Methylprednisolone

  6. Label change2026-06-11

    Label change: METHYLPREDNISOLONE (ANDA210985)

    fda · regulatory · fda · via Methylprednisolone

  7. Product recall2026-05-29

    Recall (Class II): BUDESONIDE

    fda · safety · fda · via Budesonide

  8. 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

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

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

  10. New publication2025-02-13
    Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study.

    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2025 · 4 citations · Europe PMC · via Budesonide

  11. Label change2024-12-20

    Label change: METHYLPREDNISOLONE (ANDA210985)

    fda · regulatory · fda · via Methylprednisolone

  12. Label change2024-12-20

    Label change: METHYLPREDNISOLONE (ANDA210985)

    fda · regulatory · fda · via Methylprednisolone

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.