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Protein / target

Interleukin-23 subunit alpha

Encoded byIL23AQ9NPF7Homo sapiensSwiss-Prot
UniProt: Q9NPF7Ensembl: ENSG00000110944HGNC: HGNC:15488NCBI Gene: 51561
Clinically validated
Therapeutic maturity
6
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-23 receptor binding

Strongest disease association

Psoriasis

Via encoding gene IL23A · Genetic evidence · score 0.39

Therapeutic position

Established drug target

Antibodies

Research activity

Emerging research

1 papers · latest 2006

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

Associates with IL12B to form the pro-inflammatory cytokine IL-23 that plays different roles in innate and adaptive immunity.

View complete UniProt function annotation

Associates with IL12B to form the pro-inflammatory cytokine IL-23 that plays different roles in innate and adaptive immunity (PubMed:11114383). Released by antigen-presenting cells such as dendritic cells or macrophages, binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R to activate JAK2 and TYK2 which then phosphorylate the receptor to form a docking site leading to the phosphorylation of STAT3 and STAT4 (PubMed:29287995, PubMed:32474165, PubMed:33606986). This process leads to activation of several pathways including p38 MAPK or NF-kappa-B and promotes the production of pro-inflammatory cytokines such as interleukin-17A/IL17A (PubMed:12023369). In turn, participates in the early and effective intracellular bacterial clearance (PubMed:32474165). Promotes the expansion and survival of T-helper 17 cells, a CD4-positive helper T-cell subset that produces IL-17, as well as other IL-17-producing cells (PubMed:17676044)

Subcellular location

Secreted
Domains and Gene Ontology detail (38)

Gene Ontology

  • Cendoplasmic reticulum lumen
  • Cextracellular region
  • Cextracellular space
  • Cinterleukin-23 complex
  • Fcytokine activity
  • Finterleukin-23 receptor binding
  • Pcell surface receptor signaling pathway via JAK-STAT
  • Pcell surface receptor signaling pathway via STAT
  • Pdefense response to Gram-negative bacterium
  • Pdefense response to virus
  • Pinflammatory response
  • Pinnate immune response

189 aa · 21 kDa

Biological roles

Reactome v97

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

Cell migrationGOImmune signallingUniProt · GO · Reactome
View supporting evidence

Cell migration

  • ·positive regulation of neutrophil chemotaxis

Immune signalling

  • ·Associates with IL12B to form the pro-inflammatory cytokine IL-23 that plays different r…
  • ·interleukin-23 complex
  • ·cytokine activity
  • ·interleukin-23 receptor binding
View underlying pathways (2)
Interleukin-4 and Interleukin-13 signaling
Interleukin-23 signaling

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.

IL12BIL23RIL12RB1TYK2JAK2IL12RB2IL17FIL17AIL22IL6IL23A

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

3 medicines · 5 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.

Immune System Diseases3 medicines
guselkumabmirikizumabrisankizumab
Arthritis, Psoriatic2 medicines
guselkumabrisankizumab
Psoriasis2 medicines
guselkumabrisankizumab
Colitis, Ulcerative1 medicine
mirikizumab
Crohn's Disease1 medicine
mirikizumab

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

3

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.

guselkumab
ApprovedInhibitor

Interleukin-23 inhibitor

Indicated for Arthritis, Psoriatic, Immune System Diseases, Psoriasis

Acts on a complex — shared with IL12B · 1 of 2 recorded protein targets — narrow recorded profile

mirikizumab
ApprovedInhibitor

Interleukin-23 inhibitor

Indicated for Colitis, Ulcerative, Crohn's Disease, Immune System Diseases

Acts on a complex — shared with IL12B · 1 of 2 recorded protein targets — narrow recorded profile

risankizumab
ApprovedInhibitor

Interleukin-23 inhibitor

Indicated for Arthritis, Psoriatic, Immune System Diseases, Psoriasis

Acts on a complex — shared with IL12B · 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 IL23A

Gene-level evidence surfaced through the gene IL23Athat 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.

Psoriasis
0.87Well supported

Clinical evidence dominant · Open Targets 0.68

Psoriasis vulgaris
0.81Well supported

Clinical evidence dominant · Open Targets 0.64

Colitis, Ulcerative
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Crohn's Disease
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Arthritis, Psoriatic
0.75Moderately supported

Clinical evidence dominant · Open Targets 0.60

View evidence synthesis (5)
PsoriasisWell supported
0.87
agreement 0.77–0.97
Clinical57%Genetic30%Literature11%RNA expression2%

Open Targets aggregate 0.68 · 4 independent evidence families

Psoriasis vulgarisWell supported
0.81
agreement 0.70–0.91
Clinical74%Genetic24%Literature2%

Open Targets aggregate 0.64 · 3 independent evidence families

Colitis, UlcerativeWell supported
0.76
agreement 0.62–0.89
Clinical91%RNA expression5%Literature4%

Open Targets aggregate 0.61 · 3 independent evidence families

Crohn's DiseaseWell supported
0.75
agreement 0.62–0.89
Clinical94%Literature5%RNA expression1%

Open Targets aggregate 0.61 · 3 independent evidence families

Arthritis, PsoriaticModerately supported
0.75
agreement 0.59–0.90
Clinical96%Literature4%

Open Targets aggregate 0.60 · 2 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
Psoriasis0.68
Psoriasis vulgaris0.64
Crohn's Disease0.61
Colitis, Ulcerative0.61
Arthritis, Psoriatic0.60
Immune System Diseases0.55
Pustular psoriasis0.46
Generalized pustular psoriasis0.35

Drug development

8 compounds recorded · 6 approved · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 3 drugs that target this protein in Forefront's canonical graph (3 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (8)
GUSELKUMABApproval
BRIAKINUMABApproval
USTEKINUMABApproval
EBDAROKIMABPhase 3
TILDRAKIZUMABApproval
MIRIKIZUMABApproval
BRAZIKUMABPhase 3
RISANKIZUMABApproval

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 molecules — Emerging

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

Antibodies — Strong

Approved Drug and UniProt loc high conf support this modality.

View underlying tractability evidence (5)
SM · Structure with LigandAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMM

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.

Utilization of a Cutaneous Therapy In Situ MicrodevicePHASE4

NOT_YET_RECRUITING · via risankizumab · NCT07352566

Efficacy of Top-down Therapy With Mirikizumab Versus Standard of Care With Azathioprine in Patients With Newly Diagnosed, Moderate-to-severe Crohn's Disease: A 52-week, Multicenter, Open-label, Randomized Controlled TrialPHASE4

NOT_YET_RECRUITING · via mirikizumab · NCT07659353

Optimal Care With Guselkumab In Crohn's DiseasePHASE4

RECRUITING · via guselkumab · NCT07616687

CNTO1959ISD4001: A Phase 4, Open-Label, Milk-Only Lactation Study to Assess Concentration of TREMFYA in Breast Milk of Lactating Women Who Are Receiving TREMFYA TherapeuticallyPHASE4

NOT_YET_RECRUITING · via guselkumab · NCT07654751

View all trials (26)
A Study to Evaluate Mirikizumab Concentrations in Breast Milk Following Administration of Mirikizumab by Subcutaneous Injection in Lactating Participants Receiving Mirikizumab Therapeutically for an Approved IndicationPHASE4

NOT_YET_RECRUITING · via mirikizumab · NCT07612267

INSIGHT-IBD Pragmatic Study: Investigation of Mirikizumab in Real World Settings for MirikizumabPHASE4

NOT_YET_RECRUITING · via mirikizumab · NCT07686757

Efficacy of MIrikizumab to Achieve Transmural Healing in patiENTs With Crohn's Disease : EMINENT-CDPHASE4

RECRUITING · via mirikizumab · NCT07292012

Guselkumab Intervention and Diet Evaluation for PouchitisPHASE4

RECRUITING · via guselkumab · NCT06916390

An Open-label Single-arm Study to Assess the Efficacy of Mirikizumab in Patients With Inflammatory Strictures Due to Crohn's DiseasePHASE4

RECRUITING · via mirikizumab · NCT06997965

Efficacy of Top-down Therapy With Mirikizumab Versus Standard of Care With Azathioprine in Patients With Newly Diagnosed Moderate-to-severe Ulcerative Colitis: A 52-week, Multicenter, Open-label, Randomized Controlled TrialPHASE4

RECRUITING · via mirikizumab · NCT07235904

Mirikizumab in the Treatment of Chronic Inflammatory Conditions of the PouchPHASE4

RECRUITING · via mirikizumab · NCT06864403

Evaluating the Efficacy and Safety of Mirikizumab in Adults Over 60 With Moderate to Severe Crohn's Disease and Ulcerative Colitis: A Phase IV Multicenter Interventional StudyPHASE4

NOT_YET_RECRUITING · via mirikizumab · NCT07059130

Potential Role of Guselkumab in Modulating PAIN Perception and Related Gene Pathways: a Proof-of-concept StudyPHASE4

RECRUITING · via guselkumab · NCT06974474

Immune Spatial Features of Guselkumab Cutaneous ResponsePHASE4

RECRUITING · via guselkumab · NCT05858632

Preventing Arthritis in a Multi-Center Psoriasis At-Risk CohortPHASE4

RECRUITING · via guselkumab · NCT05004727

A Phase 4, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Bio-naive Participants With Active Psoriatic Arthritis Axial DiseasePHASE4

ACTIVE_NOT_RECRUITING · via guselkumab · NCT04929210

A Phase 3 Randomized, Double-blind, and Active Controlled, Multi-center Study to Evaluate the Efficacy and Safety of JNJ-78934804 in Participants With Moderately to Severely Active Ulcerative ColitisPHASE3

RECRUITING · via guselkumab · NCT07577856

A Phase 3, Randomized, Double-blind, and Active-controlled Multicenter Study to Evaluate the Efficacy and Safety of JNJ-78934804 in Participants With Moderately to Severely Active Crohn's DiseasePHASE3

RECRUITING · via guselkumab · NCT07577843

A Phase 3b, Multicenter, Randomized, Open-Label, Active-Controlled Study to Compare the Efficacy and Safety of Guselkumab Versus Risankizumab in the Treatment of Participants With Moderately to Severely Active Crohn's DiseasePHASE3

RECRUITING · via guselkumab · NCT07499232

A Prospective, Open-Label, Randomized Controlled Study of Risankizumab (an IL-23 Inhibitor) for the Treatment of Fibrostenotic Crohn's DiseasePHASE3

NOT_YET_RECRUITING · via risankizumab · NCT07177118

A Phase 3, Multi-Center Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Risankizumab With Open-Label Induction, Randomized Double-Blind Maintenance, and Open-Label Long-Term Extension Periods in Pediatric Subjects (2 to < 18 Years of Age) With Moderately to Severely Active Ulcerative ColitisPHASE3

RECRUITING · via risankizumab · NCT07071519

A Phase 3b, Randomized, Multicenter, Controlled Study of Mirikizumab and Placebo or Mirikizumab Concomitantly Administered With Tirzepatide in Adult Participants With Moderately to Severely Active Ulcerative Colitis and Obesity or OverweightPHASE3

RECRUITING · via mirikizumab · NCT06937086

A Phase 3b, Randomized, Multicenter, Controlled Study of Mirikizumab and Placebo or Mirikizumab Concomitantly Administered With Tirzepatide in Adult Participants With Moderately to Severely Active Crohn's Disease and Obesity or OverweightPHASE3

RECRUITING · via mirikizumab · NCT06937099

Phase 3b, Multicenter, Randomized, Open-Label Study of Risankizumab Compared to Vedolizumab for the Treatment of Adult Subjects With Moderate to Severe Ulcerative Colitis Who Are Naïve to Targeted TherapiesPHASE3

ACTIVE_NOT_RECRUITING · via risankizumab · NCT06880744

CNTO1959ISD3001: A Phase 3, Multicenter, Open-label, Basket, Long-term Extension Study to Evaluate the Safety of Guselkumab in Pediatric Participants With Crohn's Disease, Ulcerative Colitis, or Juvenile Psoriatic ArthritisPHASE3

RECRUITING · via guselkumab · NCT06663332

A Phase 3, Parallel-group, Randomized, Double-blind, 4-arm, Placebo-controlled, Multicenter Study With Risankizumab as Active Reference Arm, to Investigate the Efficacy and Safety of Subcutaneous Sonelokimab in Male and Female Participants Aged 18 Years and Over With Active Psoriatic Arthritis and Previous Inadequate Response or Intolerance to Tumor Necrosis Factor-α InhibitorsPHASE3

RECRUITING · via risankizumab · NCT06641089

Open-label, Randomized, Assessor-blinded, Efficacy, Safety, Tolerability, and Pharmacokinetics Study of Subcutaneous Risankizumab With an Adalimumab Reference Arm in Children With Active Juvenile Psoriatic ArthritisPHASE3

RECRUITING · via risankizumab · NCT06100744

A Phase 3b, Open-label, Multicenter Study to Evaluate Transmural Healing and Disease Modifying Effect of Guselkumab in Crohn's Disease PatientsPHASE3

ACTIVE_NOT_RECRUITING · via guselkumab · NCT06408935

A Phase 3, Multicenter, Randomized Clinical Study to Evaluate Mirikizumab in Pediatric Crohn's DiseasePHASE3

RECRUITING · via mirikizumab · NCT05509777

A Phase 3, Multicenter, Randomized, Platform Study of p19 Inhibition of the IL-23 Pathway to Establish Efficacy in Pediatric Crohn's DiseasePHASE3

RECRUITING · via guselkumab · NCT05923073

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. Trial status changed2026-07-31

    A Phase 3 Multicenter, Open-label Study to Evaluate the Efficacy, Pharmacokinetics, Safety, and Immunogenicity of Subcutaneously Administered Ustekinumab or Guselkumab in Pediatric Participants With Active Juvenile Psoriatic Arthritis (PSUMMIT-Jr)

    Status changed to Completed · ClinicalTrials.gov · via guselkumab

  2. Trial status changed2026-07-20

    A Phase 3, Randomized, Double-Blind Study Comparing Risankizumab to Placebo in Subjects With Active Psoriatic Arthritis Including Those Who Have a History of Inadequate Response or Intolerance to Biologic Therapy(Ies) (KEEPsAKE 2)

    Status changed to Completed · ClinicalTrials.gov · via risankizumab

  3. Indication expanded2026-06-26

    Indication expansion: RISANKIZUMAB-RZAA (BLA761105)

    fda · regulatory · fda · via risankizumab

  4. Label change2026-06-26

    Label change: RISANKIZUMAB-RZAA (BLA761262)

    fda · regulatory · fda · via risankizumab

  5. Indication expanded2026-06-12

    Indication expansion: RISANKIZUMAB-RZAA (BLA761105)

    fda · regulatory · fda · via risankizumab

  6. Label change2026-06-12

    Label change: RISANKIZUMAB-RZAA (BLA761262)

    fda · regulatory · fda · via risankizumab

  7. Label change2026-03-18

    Label change: RISANKIZUMAB-RZAA (BLA761105)

    fda · regulatory · fda · via risankizumab

  8. Label change2026-03-18

    Label change: RISANKIZUMAB-RZAA (BLA761262)

    fda · regulatory · fda · via risankizumab

  9. Indication expanded2026-03-06

    Indication expansion: RISANKIZUMAB-RZAA (BLA761105)

    fda · regulatory · fda · via risankizumab

  10. Label change2026-03-06

    Label change: RISANKIZUMAB-RZAA (BLA761262)

    fda · regulatory · fda · via risankizumab

  11. Indication expanded2025-09-03

    Indication expansion: RISANKIZUMAB-RZAA (BLA761105)

    fda · regulatory · fda · via risankizumab

  12. New publication2017-01-02
    Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial.

    Journal of the American Academy of Dermatology · 2017 · 617 citations · Europe PMC · via guselkumab

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

1 papers · to 2006

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

Most cited

The IL-23/IL-17 axis in inflammation.759 cites

Iwakura Y · The Journal of clinical investigation · 2006

Recent

The IL-23/IL-17 axis in inflammation.

Iwakura Y · The Journal of clinical investigation · 2006

Europe PMC papers linked directly to this protein.