TYK2 tyrosine kinase 2
ENSG00000105397 · protein coding · Open Targets profile
Non-membrane spanning protein tyrosine kinase involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity (PubMed:10542297, PubMed:10995743, PubMed:7657660, PubMed:7813427, PubMed:8232552). Plays both structural and catalytic roles in numerous interleukins and interferons (IFN-alpha/beta) signaling (PubMed:10542297). Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6 (PubMed:10542297, PubMed:7638186). The heterodimeric cytokine receptor complexes are composed of (1) a TYK2-associated receptor chain (IFNAR1, IL12RB1, IL10RB or IL13RA1), and (2) a second receptor chain associated either with JAK1 or JAK2 (PubMed:10542297, PubMed:25762719, PubMed:7526154, PubMed:7813427). In response to cytokine-binding to receptors, phosphorylates and activates receptors (IFNAR1, IL12RB1, IL10RB or IL13RA1), creating docking sites for STAT members (PubMed:7526154, PubMed:7657660). In turn, recruited STATs are phosphorylated by TYK2 (or JAK1/JAK2 on the second receptor chain), form homo- and heterodimers, translocate to the nucleus, and regulate cytokine/growth factor responsive genes (PubMed:10542297, PubMed:25762719, PubMed:7657660). Negatively regulates STAT3 activity by promototing phosphorylation at a specific tyrosine that differs from the site used for signaling (PubMed:29162862). 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). {ECO:0000269|PubMed:10542297, ECO:0000269|PubMed:10995743, ECO:0000269|PubMed:25762719, ECO:0000269|PubMed:29162862, ECO:0000269|PubMed:7526154, ECO:0000269|PubMed:7638186, ECO:0000269|PubMed:7657660, ECO:0000269|PubMed:7813427, ECO:0000269|PubMed:8232552, ECO:0000269|PubMed:9188471}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Med-Quality Pocket, Druggable Family
- Antibody
- GO CC high conf
- PROTAC
- Literature, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.49665001034736633 (upper bound 0.6105499863624573). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 400 registry trials, updated in the last three years, of the most advanced drugs against TYK2 (delgocitinib, tofacitinib, filgotinib, upadacitinib hemihydrate, deuruxolitinib, deucravacitinib, ruxolitinib, upadacitinib, brepocitinib, peficitinib, izencitinib, cerdulatinib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Albert AssadIncyte Corporation · 4 of 4 trials Phase 2+
- Rachel B. SalitFred Hutch/University of Washington Cancer Consortium · 4 of 4 trials Phase 2+Ph2NCT04370301 · Reduced Intensity Haploidentical Transplantation for the Treatment of Primary or Secondary Myelofibrosisbrief
- Joaquin EspinosaLinda Crnic Institute for Down Syndrome · 3 of 3 trials Phase 2+
- Kathleen ButlerIncyte Corporation · 3 of 3 trials Phase 2+
- Raajit RampalMemorial Sloan Kettering Cancer Center · 2 of 3 trials Phase 2+
- Benjamin UngarIcahn School of Medicine at Mount Sinai · 2 of 2 trials Phase 2+
- Blake M WarnerNational Institute of Dental and Craniofacial Research (NIDCR) · 2 of 2 trials Phase 2+
- Gabriela HobbsMassachusetts General Hospital · 2 of 2 trials Phase 2+
- Jeffrey BerinsteinUniversity of Michigan · 2 of 2 trials Phase 2+
- Raymond ChoUniversity of California, San Francisco · 2 of 2 trials Phase 2+
- Uday PopatM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- Walter MaksymowychCARE ARTHRITIS LTD. · 2 of 2 trials Phase 2+
- Alison MoskowitzMemorial Sloan Kettering Cancer Center · 1 of 2 trials Phase 2+
- Doris PonceMemorial Sloan Kettering Cancer Center · 1 of 2 trials Phase 2+
- Michael LahniOnctura · 1 of 2 trials Phase 2+
Registry trials of delgocitinib, tofacitinib, filgotinib, upadacitinib hemihydrate, deuruxolitinib, deucravacitinib, ruxolitinib, upadacitinib, brepocitinib, peficitinib, izencitinib, cerdulatinib updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 247 of 384 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 16 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
122 trials of drugs against TYK2 were stopped early; 8 give no reason
Terminated, withdrawn and suspended interventional trials of delgocitinib, tofacitinib, filgotinib, upadacitinib hemihydrate, deuruxolitinib, deucravacitinib, ruxolitinib, upadacitinib, brepocitinib, peficitinib, izencitinib, cerdulatinib, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 122.
- terminated · 2026-09-16 · Ryvu Therapeutics SA · Ruxolitinib“Sponsor decision”
- terminated · 2026-07-16 · Bristol-Myers Squibb · matched by the registry's drug synonymsNo reason given
- terminated · 2026-07-15 · Alfasigma S.p.A. · Filgotinib“The sponsor decided to stop recruitment and to early terminate the trial with 9 enrolled patients.”
- terminated · 2026-06-26 · Incyte Corporation · matched by the registry's drug synonyms“The decision to close the study was made due to the expiration of remaining drug supply.”
- terminated · 2026-06-22 · Mayo Clinic · matched by the registry's drug synonyms“Sponsor discontinued placebo. Unable to meet enrollment goals.”
- terminated · 2026-05-29 · Beth Israel Deaconess Medical Center · Deucravacitinib“Funding withdrawn by sponsor due to funding priorities, study cannot continue without funding”
- terminated · 2026-05-20 · Psoriasis Treatment Center of Central New Jersey · Upadacitinib“There was not a big enough patient population to meet recruitment goals”
- terminated · 2026-05-06 · Mats Remberger · matched by the registry's drug synonyms“Too slow recruitment”
- terminated · 2026-04-28 · Milton S. Hershey Medical Center · Ruxolitinib 1.5% Cream“The PI left the Institution and sponsor decided to close the trial.”
- terminated · 2026-04-24 · Ohio State University Comprehensive Cancer Center · Ruxolitinib“The study was originally planned to assess four escalating DLs of ruxolitinib (upto 40 mg twice daily), but was closed early due to slow enrollment and changing treatment landscape moving towards less intense approaches.”
- terminated · 2026-04-17 · Bristol-Myers Squibb · Deucravacitinib“Business objectives have changed”
- terminated · 2026-04-07 · Children's Hospital Medical Center, Cincinnati · Ruxolitinib“Study closed due to slow enrollment.”
- terminated · 2026-04-07 · Brigham and Women's Hospital · Deucravacitinib“Sponsor terminated funding”
- terminated · 2026-03-24 · Masonic Cancer Center, University of Minnesota · Ruxolitinib 10 MG Oral Tablet“Sponsor terminated financial support”
- terminated · 2026-03-11 · Peking University First Hospital · Deucravacitinib“Terminated early due to lack of expected efficacy. Three participants were enrolled but none completed the study.”
- terminated · 2026-02-25 · Children's Hospital Medical Center, Cincinnati · Ruxolitinib“Study closed due to slow enrollment.”
- terminated · 2025-12-19 · Incyte Corporation · ruxolitinib cream“The study was terminated due to lack of enrollment.”
- withdrawn · 2025-11-24 · National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) · matched by the registry's drug synonyms“Manufacturer discontinued investigational drug supply.”
- withdrawn · 2025-11-18 · Oncology Institute of Southern Switzerland · Ruxolitinib 20 MG“Recruitment difficulty due to eligibility criteria.”
- terminated · 2025-10-29 · Incyte Corporation · Ruxolitinib“Termination of the clinical trial by sponsor.”
- terminated · 2025-10-21 · Incyte Corporation · Ruxolitinib“Study terminated due to safety issues.”
- terminated · 2025-10-21 · Incyte Corporation · ruxolitinib“The study was terminated due to futility.”
- withdrawn · 2025-10-06 · Abu Dhabi Stem Cells Center · matched by the registry's drug synonyms“Decision of the local healthcare authority”
- terminated · 2025-10-02 · St. Jude Children's Research Hospital · Ruxolitinib“Principal Investigator left institution”
- terminated · 2025-10-02 · Incyte Corporation · ruxolitinib“The study was terminated due to futility.”
Paediatric incentives and obligations for TYK2's drugs
For delgocitinib, tofacitinib, filgotinib, upadacitinib hemihydrate, deuruxolitinib, deucravacitinib, ruxolitinib, upadacitinib, brepocitinib, peficitinib, izencitinib, cerdulatinib: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: yes · TYK2 is on the list. Membership alone neither requires nor waives a pediatric study.Rule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000226763 (tofacitinib citrate, Treatment of ulcerative colitis): PM: decision on the application for modification of an agreed PIP, 14 Apr 2025; EMA/PE/0000232302 (filgotinib maleate, Treatment of chronic idiopathic arthritis (including rheumatoid arthritis, ankylosing spondylarthritis, psoriatic arthritis, and juvenile idiopathic arthritis)): PM: decision on the application for modification of an agreed PIP, 16 Apr 2025; EMA/PE/0000222532 (tofacitinib, Treatment of chronic idiopathic arthritis (including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and juvenile idiopathic arthritis)): PM: decision on the application for modification of an agreed PIP, 28 Jan 2025; EMEA-002350-PIP02-20-M01 (deucravacitinib, Treatment of chronic idiopathic arthritis (including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and juvenile idiopathic arthritis)): PM: decision on the application for modification of an agreed PIP, 13 Sept 2024; +22 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/26/3220 positive 20 Apr 2026: Treatment of systemic sclerosis; EU/3/25/3121 positive 22 Aug 2025: Treatment of idiopathic inflammatory myopathy; EU/3/14/1244 withdrawn 19 Feb 2014: Treatment of polycythaemia veraRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Jyseleca: authorised since 24 Sept 2020; Rinvoq: authorised since 16 Dec 2019; Anzupgo: authorised since 19 Sept 2024; Inijaq: opinion; +6 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of delgocitinib, tofacitinib, filgotinib, upadacitinib hemihydrate, deuruxolitinib, deucravacitinib, ruxolitinib, upadacitinib, brepocitinib, peficitinib, izencitinib, cerdulatinibRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 172 interventional studies of delgocitinib, tofacitinib, filgotinib, upadacitinib hemihydrate, deuruxolitinib, deucravacitinib, ruxolitinib, upadacitinib, brepocitinib, peficitinib, izencitinib, cerdulatinib include patients under 18; 85 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 17 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.