Protein / target

Tyrosine-protein kinase JAK1

Encoded byJAK1P23458Homo sapiensSwiss-Prot

UniProt: P23458 Ensembl: ENSG00000162434 HGNC: HGNC:6190 NCBI Gene: 3716

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Approved Drug

Protein at a glance

Biological role

Non-membrane spanning protein tyrosine kinase

Strongest disease association

Hypothyroidism

Via encoding gene JAK1 · Genetic evidence · score 0.93

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

5 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

Non-membrane spanning protein tyrosine kinase that phosphorylates signal-transducing subunits of cytokine receptor complexes like IL2RB, IL10RA, IFNAR2, IL6ST, LIFR, OSMR and IL31RA.

View complete UniProt function annotation

Non-membrane spanning protein tyrosine kinase that phosphorylates signal-transducing subunits of cytokine receptor complexes like IL2RB, IL10RA, IFNAR2, IL6ST, LIFR, OSMR and IL31RA (PubMed:11909529, PubMed:12133952, PubMed:15194700, PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552, PubMed:9188471). Functionnally, is involved in the IFN-alpha/beta/gamma signal pathway (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552). Mechanistically, in response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins (PubMed:7759950). Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors (PubMed:16239216, PubMed:32750333, PubMed:8232552). Involved in the MT-RNR2/humanin-mediated signaling pathway leading to STAT3 phosphorylation (PubMed:27384491). Binding of CNTF or the CLCF1/CLF heterodimer to CNTFR leads to IL6ST/gp130-LIFR dimerization followed by activation of JAK1 and JAK2 which in turns phosphorylate IL6ST/gp130 and LIFR (PubMed:11294841). The tyrosine phosphorylated signaling receptors serve in turn as docking proteins for STAT3 (PubMed:11294841). Involved in the oncostatin-M-mediated signaling pathway through both type I OSM receptor complex (heterodimers composed of LIFR and IL6ST) and type II OSM receptor complex (heterodimers composed of OSMR and IL6ST) (PubMed:9188471). Involved in the oncostatin-M-mediated signaling pathway through both type I OSM receptor complex (heterodimers composed of LIFR and IL6ST) and type II OSM receptor complex (heterodimers composed of OSMR and IL6ST) (PubMed:9188471). Involved in the Interleukin-31-mediated signaling pathway through the IL31 receptor complex (heterodimers composed of OSMR and IL31RA) (PubMed:15194700)

Subcellular location

Endomembrane system

Domains and Gene Ontology detail (44)

Domains & features

FERMSH2Protein kinase 1Protein kinase 2

Gene Ontology

Ccytoplasm
Ccytoplasmic side of plasma membrane
Ccytosol
Cendoplasmic reticulum lumen
Cendosome
Cextrinsic component of cytoplasmic side of plasma membrane
Cfocal adhesion
Cnucleus
Cplasma membrane
FATP binding
FCCR5 chemokine receptor binding
Fgrowth hormone receptor binding

1154 aa · 133 kDa

Biological roles

Reactome v97

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

Immune signallingUniProt · GO · ReactomeKinase signallingGOCell adhesionGO

View supporting evidence

Immune signalling

·Non-membrane spanning protein tyrosine kinase that phosphorylates signal-transducing sub…
·cytokine-mediated signaling pathway
·interleukin-10-mediated signaling pathway
·interleukin-11-mediated signaling pathway

Kinase signalling

·non-membrane spanning protein tyrosine kinase activity
·protein tyrosine kinase activity

Cell adhesion

·positive regulation of homotypic cell-cell adhesion
·protein localization to cell-cell junction

View underlying pathways (25)

Interleukin-6 signaling

MAPK3 (ERK1) activation

MAPK1 (ERK2) activation

ISG15 antiviral mechanism

Interleukin-7 signaling

Other interleukin signaling

RAF/MAP kinase cascade

Interleukin-10 signaling

Interleukin-4 and Interleukin-13 signaling

IL-6-type cytokine receptor ligand interactions

Interferon gamma signaling

Regulation of IFNG signaling

Interleukin-20 family signaling

Interleukin-15 signaling

Interleukin-35 Signalling

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.

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

2 medicines · 3 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.

Arthritis, Rheumatoid1 medicine

baricitinib

Dermatitis, Atopic1 medicine

abrocitinib

Eczema1 medicine

abrocitinib

14 medicines meet Open Targets' target-level approved-medicine definition; the 2 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

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.

abrocitinib

Narrow target profileApprovedInhibitor

Tyrosine-protein kinase JAK1 inhibitor

Indicated for Dermatitis, Atopic, Eczema

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

baricitinib

Narrow target profileApprovedInhibitor

Tyrosine-protein kinase JAK1 inhibitor

Indicated for Arthritis, Rheumatoid

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

itacitinib

Narrow target profilePhase 3Inhibitor

Tyrosine-protein kinase JAK1 inhibitor

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

delgocitinib

ApprovedInhibitor

Janus Kinase (JAK) inhibitor

Acts on a complex — shared with JAK3, JAK2, TYK2 · 1 of 4 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 JAK1

Gene-level evidence surfaced through the gene JAK1that 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.

Hypothyroidism

0.93Well supported

Genetic evidence dominant · Open Targets 0.56

Arthritis, Rheumatoid

0.92Well supported

Clinical evidence dominant · Open Targets 0.71

Autoinflammation, immune dysregulation, and eosinophilia

0.80Well supported

Genetic evidence dominant · Open Targets 0.69

Dermatitis, Atopic

0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Graft vs Host Disease

0.73Moderately supported

Clinical evidence dominant · Open Targets 0.57

View evidence synthesis (5)

HypothyroidismWell supported

0.93

agreement 0.81–1.00

Genetic100%

Open Targets aggregate 0.56 · 1 independent evidence family

Arthritis, RheumatoidWell supported

0.92

agreement 0.81–1.00

Clinical50%Genetic45%Literature5%

Open Targets aggregate 0.71 · 3 independent evidence families

Autoinflammation, immune dysregulation, and eosinophiliaWell supported

0.80

agreement 0.66–0.94

Genetic99%Literature1%Genetic literaturedup

Open Targets aggregate 0.69 · 2 independent evidence families · 1 not counted as duplicate

Dermatitis, AtopicModerately supported

0.74

agreement 0.58–0.89

Clinical96%Literature4%

Open Targets aggregate 0.60 · 2 independent evidence families

Graft vs Host DiseaseModerately supported

0.73

agreement 0.60–0.86

Clinical80%Animal model14%Literature6%

Open Targets aggregate 0.57 · 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

Arthritis, Rheumatoid0.71

Autoinflammation, immune dysregulation, and eosinophilia0.69

Dermatitis, Atopic0.60

Myelofibrosis0.59

Colitis, Ulcerative0.58

Arthritis, Psoriatic0.57

Graft vs Host Disease0.57

Hypothyroidism0.56

Crohn's Disease0.56

Drug development

25 compounds recorded · 14 approved · 11 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 (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)

RUXOLITINIB PHOSPHATEApproval

MOMELOTINIB DIHYDROCHLORIDE MONOHYDRATEApproval

NEZULCITINIBPhase 2

DEURUXOLITINIB PHOSPHATEApproval

BREPOCITINIBPhase 3

ITACITINIBPhase 3

PEFICITINIBPhase 3

SOLCITINIBPhase 2

IZENCITINIBPhase 2 3

TOFACITINIB CITRATEApproval

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 — Strong

Approved Drug and Structure with Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (go cc high conf and uniprot loc med conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

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

View underlying tractability evidence (11)

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confPR · LiteraturePR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

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 abrocitinib · NCT07352566

Prospective Evaluation of Baricitinib's Effects on Procoagulant State and Atherogenic Index in Rheumatoid Arthritis PatientsPHASE4

NOT_YET_RECRUITING · via baricitinib · NCT07357649

A Phase 3, Double-blinded, Vehicle-controlled Trial to Investigate the Efficacy and Safety of Twice Daily Delgocitinib Cream in Adult Participants With Lichen Sclerosus During a 12-Week Initial Treatment Period Followed by a 40-Week Continuation Treatment PeriodPHASE3

RECRUITING · via delgocitinib · NCT07335588

JAK Inhibitor Dose TAPering Strategy Study in Low Disease Activity Rheumatoid Arthritis PatientsPHASE4

NOT_YET_RECRUITING · via baricitinib · NCT06687551

View all trials (26)

A Pilot Study to Evaluate the Safety and Efficacy of Baricitinib in the Treatment of Frontal Fibrosing Alopecia (FFA)PHASE4

ACTIVE_NOT_RECRUITING · via baricitinib · NCT06240351

Effect of JAK Inhibitor on Bone Erosion Repair in Rheumatoid Arthritis Assessed by HR-pQCT: a Randomized Placebo-controlled StudyPHASE4

RECRUITING · via baricitinib · NCT05955066

Efficacy and Safety of Baricitinib in Systemic Sclerosis: a Phase IV, Double-blinded, Controlled Study.PHASE4

ACTIVE_NOT_RECRUITING · via baricitinib · NCT05300932

A Randomised Platform Trial to Evaluate Therapeutics in Patients With Moderate or Severe Dengue (DEN-HOST)PHASE3

NOT_YET_RECRUITING · via baricitinib · NCT07543458

Efficacy and Tolerance of Baricitinib, a JAK Inhibitor, in the Treatment of Refractory Non-infectious Non-anterior UveitisPHASE3

NOT_YET_RECRUITING · via baricitinib · NCT05651880

Safety and Efficacy of Baricitinib Combined With Acute Large Vessel Occlusion Recanalization : A Multicenter, Randomized Controlled Clinical TrialPHASE2/PHASE3

NOT_YET_RECRUITING · via baricitinib · NCT07449910

A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Baricitinib to Delay Stage 3 Type 1 Diabetes in At-risk Participants Aged ≥1 to <36 YearsPHASE3

RECRUITING · via baricitinib · NCT07222137

Justification And Evaluation of Baricitinib Plus Corticosteroids Versus corticosteroiDs Alone in pOlymyalgia RhEumatica - JADORE-BARI StudyPHASE3

RECRUITING · via baricitinib · NCT07279688

A Phase 3, Multicenter, Long-Term, Open Label Study Evaluating the Safety and Efficacy of Abrocitinib, With or Without Topical Medications Administered to Pediatric Participants Aged 2 Years and Older With Moderate-to-Severe Atopic DermatitisPHASE3

RECRUITING · via abrocitinib · NCT06807281

A 16-WEEK, MULTICENTER, INTERVENTIONAL, PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO INVESTIGATE EFFICACY AND SAFETY OF ABROCITINIB IN CHILDREN 6 TO LESS THAN 12 YEARS OF AGE WITH MODERATE-TO-SEVERE ATOPIC DERMATITISPHASE3

RECRUITING · via abrocitinib · NCT06807268

Serum s100B in Generalized Vitiligo and Its Relation to Oral Baricitinib, Narrow Band Ultraviolet (B) TherapyPHASE2/PHASE3

RECRUITING · via baricitinib · NCT06768840

Safety and Efficacy of Baricitinib on Skin Tightening in Diffuse Cutaneous Systemic Sclerosis: A Comparative Study With MethotrexatePHASE3

RECRUITING · via baricitinib · NCT06936215

Prospective Pilot Study of the Clinical Efficacy and Safety of the Method for Preventing a Graft-versus-host Disease Through the Agency of Using the Combination of Post-transplantation Cyclophosphamide With Abatacept, Vedolizumab and Baricitinib at Children and Young Adults With Hemoblastosis After Hematopoietic Stem Cell Transplantation From an Unrelated or Haploidentic DonorPHASE2/PHASE3

ACTIVE_NOT_RECRUITING · via baricitinib · NCT06475820

Baricitinib in Patients With Relapsing or naïve Dermatomyositis: a Multicenter Randomized Controlled Trial (BIRD)PHASE3

RECRUITING · via baricitinib · NCT04972760

Combination of Baricitinib and Anti-TNF vs. Baricitinib in Patients With Rheumatoid Arthritis: a Randomized Controlled Phase III TrialPHASE3

ACTIVE_NOT_RECRUITING · via baricitinib · NCT04870203

Randomised Evaluation of COVID-19 TherapyPHASE3

RECRUITING · via baricitinib · NCT04381936

An Open-label, Active-Controlled, Safety, and Efficacy Study of Oral Baricitinib in Patients From 2 Years to Less Than 18 Years Old With Active Juvenile Idiopathic Arthritis-Associated Uveitis or Chronic Anterior Antinuclear Antibody-Positive UveitisPHASE3

ACTIVE_NOT_RECRUITING · via baricitinib · NCT04088409

Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired PneumoniaPHASE3

RECRUITING · via baricitinib · NCT02735707

Treatment of Rheumatoid Arthritis With Disease-modifying Antirheumatic Drugs (DMARDs): Predictors of ResponsePHASE3

RECRUITING · via baricitinib · NCT03414502

Phase 2 Open Label Trial of Delgocitinib 20 mg/g Cream in Subjects With Frontal Fibrosing Alopecia (FFA)PHASE2

NOT_YET_RECRUITING · via delgocitinib · NCT07671157

Baricitinib Curative Repression of HIV-1PHASE2

NOT_YET_RECRUITING · via baricitinib · NCT07209267

TPO-RA Plus Baricitinib vs. TPO-RA in Patients With ITP : A Randomized, Open-label TrialPHASE2

NOT_YET_RECRUITING · via baricitinib · NCT07669675

JAK Signaling in Depression and Cognition in Male Football PlayersPHASE2

NOT_YET_RECRUITING · via baricitinib · NCT07608796

A Pilot Study to Assess Safety and Biomarker Responses of Delgocitinib (JAK1,2,3/TYK2 Inhibitor) in Central Centrifugal Cicatricial Alopecia and Lichen PlanopilarisPHASE2

RECRUITING · via delgocitinib · NCT07487948

PALETTE- Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Exploratory, Bayesian Basket TrialPHASE2

NOT_YET_RECRUITING · via baricitinib · NCT06381661

Immunotherapy With a JAK1/JAK2 Inhibitor (Baricitinib) and an mTORC1 Inhibitor (Sirolimus), Alone and in Combination, for the Control of HIV-1 Replication After Antiretroviral Treatment Interruption: a Phase II Multicenter, Multi-arm, Multi-stage, Randomized, Double-blind, Placebo-controlled, Adaptative TrialPHASE2

NOT_YET_RECRUITING · via baricitinib · NCT07081763

ClinicalTrials.gov via the drug-target graph.

What's happening now

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.

Label change2026-06-30
Label change: ABROCITINIB (NDA213871)
fda · regulatory · fda · via abrocitinib
Label change2026-06-30
Label change: BARICITINIB (NDA207924)
fda · regulatory · fda · via baricitinib
Label change2026-06-30
Label change: DELGOCITINIB (NDA219155)
fda · regulatory · fda · via delgocitinib
Regulatory approval2025-07-23
Approval: DELGOCITINIB (NDA219155)
fda · regulatory · fda · via delgocitinib
New publication2025-04-16
Efficacy and safety of topical delgocitinib cream versus oral alitretinoin capsules in adults with severe chronic hand eczema (DELTA FORCE): a 24-week, randomised, head-to-head, phase 3 trial.
Lancet (London, England) · 2025 · 12 citations · Europe PMC · via delgocitinib
Regulatory approval2024-09-19
Approval: Anzupgo (EMA)
ema · regulatory · ema · via delgocitinib
Indication expanded2023-12-14
Indication expansion: ABROCITINIB (NDA213871)
fda · regulatory · fda · via abrocitinib
Indication expanded2023-02-09
Indication expansion: ABROCITINIB (NDA213871)
fda · regulatory · fda · via abrocitinib
New publication2021-01-01
Immunopathogenesis and treatment of cytokine storm in COVID-19.
Theranostics · 2021 · 308 citations · Europe PMC · via baricitinib
Safety communication2020-08-26
Drug Safety Update: Baricitinib (Olumiant▼): increased risk of diverticulitis, particularly in patients with risk factors
mhra · safety · mhra · via baricitinib
New publication2020-07-01
Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.
Lancet (London, England) · 2020 · 337 citations · Europe PMC · via abrocitinib
Safety communication2020-03-18
Drug Safety Update: Baricitinib (Olumiant▼): risk of venous thromboembolism
mhra · safety · mhra · via baricitinib

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.