JAK2 Janus kinase 2
ENSG00000096968 · protein coding · Open Targets profile
Non-membrane spanning protein tyrosine kinase that phosphorylates type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin receptor (MPL/TPOR); or type II receptors including IFN-alpha, IFN-beta, IFN- gamma and multiple interleukins (PubMed:15690087, PubMed:15899890, PubMed:7615558, PubMed:9188471, PubMed:9657743). Functionally, plays a pivotal role in signal transduction and is involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. Mechanistically, following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:15690087, PubMed:9618263). 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, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain (PubMed:9657743). Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin (PubMed:19783980). Up- regulates the potassium voltage-gated channel activity of KCNA3 (PubMed:25644777). 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). {ECO:0000269|PubMed:11294841, ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:15690087, ECO:0000269|PubMed:19783980, ECO:0000269|PubMed:20098430, ECO:0000269|PubMed:21368206, ECO:0000269|PubMed:21423214, ECO:0000269|PubMed:25644777, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:9188471, ECO:0000269|PubMed:9618263, ECO:0000269|PubMed:9657743}.
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
- PROTAC
- Literature, UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.6174499988555908 (upper bound 0.7387099862098694). 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 JAK2 (fedratinib, upadacitinib hemihydrate, tofacitinib, lestaurtinib, pacritinib, filgotinib, deuruxolitinib, delgocitinib, momelotinib dihydrochloride monohydrate, ruxolitinib, upadacitinib, baricitinib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- 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
- Andrew H MillerEmory University · 3 of 3 trials Phase 2+
- Joaquin EspinosaLinda Crnic Institute for Down Syndrome · 3 of 3 trials Phase 2+
- Raajit RampalMemorial Sloan Kettering Cancer Center · 2 of 3 trials Phase 2+
- Anna HalpernFred Hutch/University of Washington Cancer Consortium · 2 of 2 trials Phase 2+
- Blake M WarnerNational Institute of Dental and Craniofacial Research (NIDCR) · 2 of 2 trials Phase 2+
- Cornelia D CudriciNational Heart, Lung, and Blood Institute (NHLBI) · 2 of 2 trials Phase 2+
- Deepak KilariMedical College of Wisconsin · 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+
- Jennifer FelgerEmory University · 2 of 2 trials Phase 2+
- Najla El JurdiNational Cancer Institute (NCI) · 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+
- Abdulraheem YacoubUniversity of Kansas School of Medicine · 1 of 2 trials Phase 2+
Registry trials of fedratinib, upadacitinib hemihydrate, tofacitinib, lestaurtinib, pacritinib, filgotinib, deuruxolitinib, delgocitinib, momelotinib dihydrochloride monohydrate, ruxolitinib, upadacitinib, baricitinib 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; 272 of 382 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. 18 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
144 trials of drugs against JAK2 were stopped early; 14 give no reason
Terminated, withdrawn and suspended interventional trials of fedratinib, upadacitinib hemihydrate, tofacitinib, lestaurtinib, pacritinib, filgotinib, deuruxolitinib, delgocitinib, momelotinib dihydrochloride monohydrate, ruxolitinib, upadacitinib, baricitinib, 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 144.
- withdrawn · 2026-11-05 · Incepta Pharmaceuticals Ltd · Baricitinib“The study was planned during COVID-19 outbreak to assess Baricitinib in Patients With Moderate and Severe COVID-19. The study could not be started due to many obstacle which was raised because of Pandemic. The study is no more relevant.”
- terminated · 2026-09-16 · Ryvu Therapeutics SA · Ruxolitinib“Sponsor decision”
- withdrawn · 2026-09-09 · Vanderbilt University Medical Center · Baricitinib 4 MG“This submission for the pilot study has been withdrawn as the full trial opened under a different NCT number before participants enrolled in the pilot.”
- withdrawn · 2026-08-17 · Thomas Jefferson University · Pacritinib“FDA requested significant changes to the study protocol”
- terminated · 2026-08-11 · Bristol-Myers Squibb · matched by the registry's drug synonymsNo reason given
- terminated · 2026-08-11 · Eli Lilly and Company · Baricitinib“Study terminated due to an inability to enroll participants.”
- 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 · 2026-05-26 · The University of Texas Health Science Center at San Antonio · pacritinib“Investigational drug limitations”
- 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.”
- terminated · 2025-12-04 · H. Lee Moffitt Cancer Center and Research Institute · Fedratinib Pill“Did not advance to Phase 2”
- withdrawn · 2025-11-18 · Oncology Institute of Southern Switzerland · Ruxolitinib 20 MG“Recruitment difficulty due to eligibility criteria.”
- terminated · 2025-11-17 · Medical College of Wisconsin · Pacritinib“futility and drug supplier in favor of new metastatic protocol.”
- 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”
Paediatric incentives and obligations for JAK2's drugs
For fedratinib, upadacitinib hemihydrate, tofacitinib, lestaurtinib, pacritinib, filgotinib, deuruxolitinib, delgocitinib, momelotinib dihydrochloride monohydrate, ruxolitinib, upadacitinib, baricitinib: 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 · JAK2 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/0000236886 (baricitinib, Prevention of stage 3 type 1 diabetes mellitus): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 10 Sept 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; +24 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/3/26/3223 positive 20 Apr 2026: Treatment of VEXAS syndrome; EU/3/11/888 positive 5 Aug 2011: Treatment of primary myelofibrosis; EU/3/11/886 positive 5 Aug 2011: Treatment of post-polycythaemia vera myelofibrosis; +6 moreRule: 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; Olumiant: authorised since 13 Feb 2017; +8 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 fedratinib, upadacitinib hemihydrate, tofacitinib, lestaurtinib, pacritinib, filgotinib, deuruxolitinib, delgocitinib, momelotinib dihydrochloride monohydrate, ruxolitinib, upadacitinib, baricitinibRule: 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 · 194 interventional studies of fedratinib, upadacitinib hemihydrate, tofacitinib, lestaurtinib, pacritinib, filgotinib, deuruxolitinib, delgocitinib, momelotinib dihydrochloride monohydrate, ruxolitinib, upadacitinib, baricitinib include patients under 18; 95 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 31 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.