JAK3 Janus kinase 3
ENSG00000105639 · protein coding · Open Targets profile
Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A and STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion. {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:20440074, ECO:0000269|PubMed:7662955, ECO:0000269|PubMed:8022485}.
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 Withdrawn means the drug was pulled from the market or from development.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, High-Quality Pocket, Druggable Family
- Antibody
- GO CC high conf, UniProt loc med conf, Human Protein Atlas loc
- PROTAC
- Literature, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.7285699844360352 (upper bound 0.8698499798774719). 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 JAK3 (ritlecitinib, filgotinib, delgocitinib, upadacitinib hemihydrate, tofacitinib, deuruxolitinib, upadacitinib, ruxolitinib, peficitinib, AT-9283, izencitinib, decernotinib), 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+
- Farhad Ravandi-KashaniM.D. Anderson Cancer Center · 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+
- Srdan VerstovsekM.D. Anderson Cancer Center · 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+
- Xuefeng Hedepartment of hematology, The First Affiliated Hospital of Soochow University · 2 of 2 trials Phase 2+
- Alison MoskowitzMemorial Sloan Kettering Cancer Center · 1 of 2 trials Phase 2+
Registry trials of ritlecitinib, filgotinib, delgocitinib, upadacitinib hemihydrate, tofacitinib, deuruxolitinib, upadacitinib, ruxolitinib, peficitinib, AT-9283, izencitinib, decernotinib 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; 252 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.
113 trials of drugs against JAK3 were stopped early; 8 give no reason
Terminated, withdrawn and suspended interventional trials of ritlecitinib, filgotinib, delgocitinib, upadacitinib hemihydrate, tofacitinib, deuruxolitinib, upadacitinib, ruxolitinib, peficitinib, AT-9283, izencitinib, decernotinib, 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 113.
- 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 · 2026-05-20 · 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 · 2026-04-07 · Children's Hospital Medical Center, Cincinnati · Ruxolitinib“Study closed due to slow enrollment.”
- terminated · 2026-03-24 · Masonic Cancer Center, University of Minnesota · Ruxolitinib 10 MG Oral Tablet“Sponsor terminated financial support”
- 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 · 2025-12-09 · Ahuva D Cices · Ritlecitinib“Sponsor terminated study”
- 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.”
- terminated · 2025-08-29 · Chia Tai Tianqing Pharmaceutical Group Co., Ltd. · matched by the registry's drug synonyms“This study was closed due to business reasons. Closure was not prompted by any safety or efficacy concerns.”
- terminated · 2025-08-07 · Novartis Pharmaceuticals · Ruxolitinib“Sponsor Decision”
- terminated · 2025-07-18 · Icahn School of Medicine at Mount Sinai · Ritlecitinib“No significant improvement in disease as graded by our assessments.”
- terminated · 2025-07-11 · Pfizer · matched by the registry's drug synonyms“For business reasons”
Paediatric incentives and obligations for JAK3's drugs
For ritlecitinib, filgotinib, delgocitinib, upadacitinib hemihydrate, tofacitinib, deuruxolitinib, upadacitinib, ruxolitinib, peficitinib, AT-9283, izencitinib, decernotinib: 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 · JAK3 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/0000236669 (ritlecitinib, Treatment of vitiligo): 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; EMEA-002451-PIP02-21 (ritlecitinib, Treatment of ulcerative colitis): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 10 Aug 2022; +21 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/3/14/1244 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; Litfulo: authorised since 15 Sept 2023; +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 ritlecitinib, filgotinib, delgocitinib, upadacitinib hemihydrate, tofacitinib, deuruxolitinib, upadacitinib, ruxolitinib, peficitinib, at-9283, izencitinib, decernotinibRule: 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 · 180 interventional studies of ritlecitinib, filgotinib, delgocitinib, upadacitinib hemihydrate, tofacitinib, deuruxolitinib, upadacitinib, ruxolitinib, peficitinib, at-9283, izencitinib, decernotinib include patients under 18; 87 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 20 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.