JAK1 is one of the kinases that pass cytokine and interferon signals inside immune and blood cells. Ruxolitinib and momelotinib block JAK1 together with JAK2 to calm the inflammation of myelofibrosis; golidocitinib is the first JAK1-only inhibitor approved for a cancer, in peripheral T-cell lymphoma. This dossier gathers the 3 products (3 approved), 16 trials, 0 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Biology
The JAK-STAT pathway record notes that interferon-gamma signalling through JAK1/2 and STAT1 raises MHC and PD-L1 expression, and that JAK1/2 loss-of-function mutations cause acquired resistance to PD-1 blockade, so JAK1 is both a drug target in blood cancers and a resistance gene in immunotherapy.
- Myelofibrosis and other myeloproliferative neoplasms (JAK1/2 inhibitors)
- Peripheral T-cell lymphoma (golidocitinib)
- Tumours with JAK1 loss (checkpoint resistance)
External identifiers
Built from HGNC, Ensembl, UniProt and ChEMBL idsProducts by modality and phase
Browse products →| Modality | Approved |
|---|---|
| Small molecule 3 |
Trials
Evidence ranking →| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
MANIFEST-2 NCT04603495 | 3 | Mixed | JAK inhibitor-naive myelofibrosis: ruxolitinib with the BET inhibitor pelabresib or placebo | Pelabresib plus ruxolitinib roughly doubled the week-24 spleen volume response over ruxolitinib alone; the symptom endpoint did not reach significance. | |
MOMENTUM NCT04173494 | 3 | Positive | Symptomatic, anaemic myelofibrosis previously treated with a JAK inhibitor: momelotinib against danazol | Momelotinib improved symptom response, transfusion independence and spleen response compared with danazol; approved in September 2023. | |
RESPONSE-2 NCT02038036 | 3 | Positive | Hydroxyurea-resistant or intolerant polycythaemia vera without splenomegaly: ruxolitinib versus best available therapy | Haematocrit control at week 28: 62% vs 19%. | |
RESPONSE NCT01243944 | 3 | Positive | Polycythaemia vera resistant to or intolerant of hydroxyurea, with an enlarged spleen: ruxolitinib versus best available therapy | Composite response at week 32: 21% vs 1%; haematocrit control 60% vs 20%. | |
COMFORT-I NCT00952289 | 3 | Positive | Intermediate-2 or high-risk primary myelofibrosis, post-polycythaemia vera or post-essential thrombocythaemia myelofibrosis: twice-daily oral ruxolitinib or placebo, with spleen volume by MRI at 24 weeks as the primary endpoint | Spleen volume reduction of 35 percent or more at 24 weeks in 41.9 percent of patients on ruxolitinib against 0.7 percent on placebo; approved in the United States in November 2011. | |
COMFORT-II NCT00934544 | 3 | Positive | Intermediate-2 or high-risk primary myelofibrosis, post-polycythaemia vera or post-essential thrombocythaemia myelofibrosis: open-label ruxolitinib against best available therapy chosen by the physician, with spleen volume at 48 weeks as the primary endpoint | Spleen volume reduction of at least 35 percent at week 48 in 28 percent of patients on ruxolitinib against 0 percent on best available therapy; European approval in 2012. | |
| 3 | Recruiting | A Phase 3, Open-Label, Randomized, Multinational Study to Investigate the Anti-tumor Efficacy of Golidocitinib Versus Investigator's Choice in Adult Patients With Relapsed/Refractory Peripheral T-cell Lymphoma | - | ||
| 3 | Active | A Phase 1/3 Study to Evaluate Efficacy and Safety of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Ruxolitinib in Treatment-naïve Patients With Myelofibrosis | - | ||
| MAJIC-PV | 2 | Positive | Hydroxyurea-resistant or intolerant polycythaemia vera: ruxolitinib versus best available therapy | Complete response within 1 year: 43% vs 26%; complete response associated with better event-free survival. | |
| MAJIC-ET | 2 | Negative | Hydroxyurea-resistant or intolerant essential thrombocythaemia: ruxolitinib versus best available therapy | Complete response within 1 year 46.6% (ruxolitinib) vs 44.2% (best available therapy), not significant; no difference in clots, bleeding or transformation at 2 years. | |
AALL1521 NCT02723994 | 2 | Completed | Children and young adults with newly diagnosed high-risk Philadelphia chromosome-like B-cell acute lymphoblastic leukaemia carrying a CRLF2 rearrangement or a JAK pathway mutation: the JAK1 and JAK2 inhibitor ruxolitinib added to post-induction chemotherapy, in a dose-finding part and an efficacy part with three-year event-free survival as the endpoint | - | |
| 2 | Active | An Open-Label, Multicenter, Rollover Study to Enable Continued Treatment Access for Subjects Previously Enrolled in Studies of Ruxolitinib | - | ||
| 2 | Active | A Two-Part, Randomized, Open-label, Multicenter, Phase 2a/2b Study of the Efficacy, Safety, and Pharmacokinetics of KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera | - | ||
| 2 | Active | A Phase 2, Open-Label, Multicenter, Rollover Study to Provide Continued Treatment for Participants With B-Cell Malignancies Previously Enrolled in Studies of Parsaclisib (INCB050465) | - | ||
| 1/2 | Active | A Phase 1b/2 Study of BMS-986158 Monotherapy and in Combination With Either Ruxolitinib or Fedratinib in Participants With DIPSS-Intermediate or High Risk Myelofibrosis | - | ||
| 1/2 | Recruiting | A Phase I/II Clinical Study to Evaluate the Efficacy and Safety of GW5282 in Combination With Golidocitinib in the Treatment of T-Cell Lymphoma | - |
Resistance routes
Unaddressed routes →The resistance atlas has no route that names this target.
Pathways
Pathway-to-drug matrix →No pathway diagram carries this target as a node.
Companion diagnostics
Assay registry →No companion diagnostic in the registry measures this target.
Preclinical models
All models →No model entry for this target yet; check the cancer entries on the models page.
Open questions
All open questions →No open questions recorded for this target yet. Suggest one.
Ideas and companies
Literature
Preprints →Query for this target: (TITLE:"JAK1" OR ABSTRACT:"JAK1" OR TITLE:"Janus kinase 1" OR ABSTRACT:"Janus kinase 1" OR TITLE:"JAK1A" OR ABSTRACT:"JAK1A" OR TITLE:"JTK3" OR ABSTRACT:"JTK3") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about JAK1, not a curated reading list.
Export
The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/jak1.json. Licence CC BY-NC 4.0.