JAK1
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.
Overview
JAK1 (chromosome 1p31.3) is a non-receptor tyrosine kinase that phosphorylates the signal-transducing subunits of cytokine receptor complexes including IL2RB, IL10RA, IFNAR2, IL6ST, LIFR, OSMR and IL31RA; it is required for interferon alpha, beta and gamma signalling, where it phosphorylates IFNAR2 to create STAT docking sites, and it activates STATs directly or through partner JAK kinases (UniProt P23458). In OnCo, JAK1 is inhibited with JAK2 by ruxolitinib and momelotinib for spleen and symptom control in myelofibrosis, deliberately spared by pacritinib to limit myelosuppression, and selectively targeted by golidocitinib, approved in China in 2024 for relapsed peripheral T-cell lymphoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
3 products aim at JAK1: small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
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)
Golidocitinib is Dizal's JAK1 inhibitor, approved in China in 2024 as the first JAK inhibitor for relapsed peripheral T-cell lymphoma, a cancer with few options after first-line chemotherapy.
Momelotinib is the JAK inhibitor designed for anaemic myelofibrosis patients: it can improve haemoglobin while shrinking the spleen.
Ruxolitinib was the first JAK inhibitor: it shrinks the spleen and relieves symptoms in myelofibrosis and controls blood counts in polycythaemia vera, without eliminating the disease clone.
Notes
top- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.
Latest papers
topQuery 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.
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