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Protein / target

Interleukin-6

Encoded byIL6P05231Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

Interleukin-6 receptor binding

Strongest disease association

Asthma

Via encoding gene IL6 · Genetic evidence · score 0.86

Therapeutic position

Established drug target

Antibodies

Research activity

Actively researched

65 papers · latest 2024

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

Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism.

View complete UniProt function annotation

Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway (Probable). The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable)

Subcellular location

Secreted
Domains and Gene Ontology detail (102)

Gene Ontology

  • Cendoplasmic reticulum lumen
  • Cextracellular region
  • Cextracellular space
  • Cinterleukin-6 receptor complex
  • Cplasma membrane
  • Fcytokine activity
  • Fgrowth factor activity
  • Fidentical protein binding
  • Finterleukin-6 receptor binding
  • Pacute-phase response
  • Pautocrine signaling
  • Pcell surface receptor signaling pathway via JAK-STAT

212 aa · 24 kDa

Biological roles

Reactome v97

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

Cell proliferation & survivalGOCell migrationGOImmune signallingUniProt · GO · ReactomeTranscriptional regulationGO · ReactomeApoptosis & cell deathGOHaemostasisGO
View supporting evidence

Cell proliferation & survival

  • ·negative regulation of cell population proliferation
  • ·positive regulation of cell population proliferation

Cell migration

  • ·monocyte chemotaxis
  • ·positive regulation of leukocyte chemotaxis

Immune signalling

  • ·Cytokine with a wide variety of biological functions in immunity, tissue regeneration, a…
  • ·interleukin-6 receptor complex
  • ·cytokine activity
  • ·interleukin-6 receptor binding

Transcriptional regulation

  • ·positive regulation of DNA-templated transcription
  • ·positive regulation of gene expression
  • ·positive regulation of miRNA transcription
  • ·positive regulation of transcription by RNA polymerase II

Apoptosis & cell death

  • ·negative regulation of apoptotic process
  • ·neutrophil apoptotic process
  • ·positive regulation of apoptotic process
  • ·positive regulation of type B pancreatic cell apoptotic process

Haemostasis

  • ·platelet activation
  • ·positive regulation of platelet aggregation
View underlying pathways (13)

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.

IL6RIL2IL6STIL3IL1R1TNFRSF…IL10IL1BJAK1JAK2IL6

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

1 medicine · 1 area

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.

Immune System Diseases1 medicine

3 medicines meet Open Targets' target-level approved-medicine definition; the 1 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.

ziltivekimab
Narrow target profilePhase 3Inhibitor

Interleukin-6 inhibitor

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

siltuximab
Narrow target profileApprovedAntagonist

Interleukin-6 antagonist

Indicated for Immune System Diseases

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

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 IL6

Gene-level evidence surfaced through the gene IL6that 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.

Asthma
0.89Well supported

Genetic evidence dominant · Open Targets 0.56

Aortic Valve Stenosis
0.82Well supported

Genetic evidence dominant · Open Targets 0.51

Atherosclerosis
0.79Well supported

Genetic evidence dominant · Open Targets 0.47

Arthritis, Rheumatoid
0.78Well supported

Clinical evidence dominant · Open Targets 0.52

COVID-19
0.77Well supported

Genetic evidence dominant · Open Targets 0.44

View evidence synthesis (5)
AsthmaWell supported
0.89
agreement 0.781.00
Genetic77%Literature13%Clinical10%

Open Targets aggregate 0.56 · 3 independent evidence families

Aortic Valve StenosisWell supported
0.82
agreement 0.690.96
Genetic95%Literature5%

Open Targets aggregate 0.51 · 2 independent evidence families

AtherosclerosisWell supported
0.79
agreement 0.690.90
Genetic58%Clinical31%Literature11%

Open Targets aggregate 0.47 · 3 independent evidence families

Arthritis, RheumatoidWell supported
0.78
agreement 0.670.90
Clinical44%Genetic literature43%Literature13%

Open Targets aggregate 0.52 · 3 independent evidence families

COVID-19Well supported
0.77
agreement 0.660.88
Genetic48%Clinical38%Literature14%

Open Targets aggregate 0.44 · 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
Asthma0.56
Arthritis, Rheumatoid0.52
Immune System Diseases0.51
Aortic Valve Stenosis0.51
Atherosclerosis0.47
Aortic valve calcification0.46
Kaposi sarcoma, susceptibility to0.46
COVID-190.44
Atrial Fibrillation0.43

Drug development

6 compounds recorded · 3 approved · 3 in clinical development

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 (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (6)
SILTUXIMABApproval
OLOKIZUMABApproval
ZILTIVEKIMABPhase 3
CLAZAKIZUMABPhase 3
SIRUKUMABApproval
PACIBEKITUGPhase 2

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 moleculesEmerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

AntibodiesStrong

Approved Drug and UniProt loc high conf support this modality.

Protein degradersEmerging

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

View underlying tractability evidence (9)
SM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of transcription factor activityToxCastregulation of gene expressionToxCastdepressionClinPGx

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)

RECRUITING · via siltuximab · NCT05684692

UNKNOWN · via siltuximab · NCT02796859

ClinicalTrials.gov via the drug-target graph.

What's happening now

2

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. New publication2021-05-17
    Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease.

    Circulation research · 2021 · 459 citations · Europe PMC · via ziltivekimab

  2. Accelerated approval granted2014-05-22

    Accelerated approval: Sylvant (EMA)

    ema · regulatory · ema · via siltuximab

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.

Research activity

65 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Tanaka T · Cold Spring Harbor perspectives in biology · 2014

Heinrich PC · The Biochemical journal · 1990

Smith SE · The Journal of neuroscience : the official journal of the Society for Neuroscience · 2007

Landskron G · Journal of immunology research · 2014

Recent

Europe PMC papers linked directly to this protein.