Janus kinases (or JAKs) are a family of tyrosine kinases that are associated with cytokine receptors. Upon receptor activation JAKs phosphorylate the transcription factors known as STATs and initiate the JAK-STAT signaling pathway. Four JAK family members have been identified.

Pathways (1)
Gene Data

JAK Inhibitors

Cat. No. Product Name / Activity
0414 AG 490
JAK2, JAK3 inhibitor. Also EGFR-kinase inhibitor
5617 AZD 1480
Potent and selective JAK2 inhibitor; antiangiogenic
7222 Baricitinib
Highly potent JAK1 and JAK2 inhibitor; also inhibits JAK3 and Tyk2
4500 Cercosporamide
Potent Mnk2 inhibitor; also inhibits JAK3
4556 CP 690550 citrate
Potent JAK inhibitor
1571 Cucurbitacin I
Selective inhibitor of STAT3/JAK2 signaling
3395 Lestaurtinib
JAK2, FLT3 and TrkA inhibitor; also inhibits AurA and AurB
6506 PF 06551600 malonate
Potent and selective JAK3 inhibitor
6577 Pyridone 6
Potent pan-JAK inhibitor; induces intermediate mesoderm; cell-permeable
7064 Ruxolitinib
Potent and selective JAK1/JAK2 inhibitor; orally bioavailable
7048 Ruxolitinib phosphate
Phosphate salt of Ruxolitinib (Cat. No. 7064); potent and selective JAK1/JAK2 inhibitor
3035 SD 1008
JAK2/STAT3 signaling pathway inhibitor
6125 TC JL 37
Potent TYK2 inhibitor
4221 TCS 21311
Potent JAK3 inhibitor. Also inhibits GSK-3β and PKC
7783 Upadacitinib
JAK1-selective inhibitor
3115 WHI-P 154
JAK3 kinase inhibitor. Also inhibits EGFR
1367 ZM 39923 hydrochloride
Potent, selective JAK3 inhibitor


Cat. No. Product Name / Activity
7675 SJ 1008030
Selective JAK2 Degrader (PROTAC®)
7727 SJ 10542
Potent and selective JAK2/3 Degrader (PROTAC®)

Janus kinases (or JAKs) are a family of nonreceptor tyrosine kinases that function downstream of cytokine receptors. Following activation of a cytokine receptor JAKs phosphorylate the transcription factors known as STATs and initiate the JAK-STAT signaling pathway. Four JAK family members have been identified (JAK1, JAK2, JAK3 and Tyk2), which share a similar protein domain structure: a kinase domain (JH1), a 'pseudo'-kinase domain that regulates the kinase activity of JH1, a SH2 domain and an NH2-terminal domain known as the FERM domain.

The FERM domain of Janus kinase family members mediates the association of JAK with other enzymes and cytokine receptors. The JAK Tyk2 associates with the IFN-1, IL-6, 10, 12, and 23 cytokine receptor families. JAK1 mediates signals from IFN-α,β,γ and IL-2, 6 receptors. JAK2 transduces signals from the single chain and IL-3 cytokine receptor families, and from the IFN-γ receptors. JAK3 associates with the IL-2 receptor γ-chain.

Janus Kinases and Inflammation

JAK/STAT signaling mediates the effects of a wide range of inflammatory cytokines. JAK inhibitors have been approved for the treatment of inflammatory and autoimmune diseases, including baricitinib (Cat. No. 7222) for rheumatoid arthritis and ruxolitinib (Cat. No. 7064) for graft-versus-host disease.

The JAK/STAT pathway is implicated in the cytokine storm (also known as cytokine release syndrome) associated with severe infection, particularly COVID-19. IL-6, an important mediator of cytokine storm, activates JAK/STAT signaling via two separate mechanisms termed cis and trans signaling pathways. The cis signaling pathway, involves the activation of JAK and STAT3 via membrane-bound IL-6 receptors (mIL-6R) and gp130 receptors and has multiple effects on the innate and adaptive immune systems, while the trans signaling pathway activates JAK/STAT3 signaling in cells that express gp130 but not mIL-6R, such as endothelial cells. These actions result in increased cytokine production and contribute to the poor clinical outcomes associated with COVID-19. Baricitinib and ruxolitinib have both been investigated for their potential to reduce the cytokine storm in COVID-19 patients.

The Role of Janus Kinases in Cytokine Storm

IL-6 and JAK/STAT signaling in Cytokine Storm

Figure 1: Schematic highlighting the role of the JAK/STAT-Signaling pathway in the perpetuation of cytokine storm. Activated immune cells release cytokines including interleukin-6, which activates JAK/STAT signaling via two separate pathways, known as trans- and cis-signaling, leading to further cytokine release. Adapted from More & June (2020) Cytokine release syndrome in severe COVID-19. Science 368 473.

Janus Kinases and Cancer

In addition to its role in inflammation, the IL-6/JAK/STAT signaling axis is also associated with certain cancers, particularly myeloproliferative neoplasms (MPN). Abnormal hyperactivation of the pathway drives tumor proliferation, invasiveness and metastasis, as well as immune evasion.

JAK2 also has a role as an Epigenetic Writer, that is an enzyme that catalyzes the addition of chemical groups to histone tails, as it is involved in the phosphorylation of histone proteins. This key epigenetic modification results in changes in chromatin architecture and therefore gene expression.

External sources of pharmacological information for JAK :

    Pathways for JAK

    JAK-STAT Signaling Pathway

    JAK-STAT Signaling Pathway

    The JAK-STAT signaling pathway has several roles, including the control of cell proliferation and hematopoiesis. It is the main signal transduction cascade from cytokine receptors.

    JAK Gene Data

    Gene Species Gene Symbol Gene Accession No. Protein Accession No.
    JAK1 Human JAK1 NM_002227 P23458
    Mouse Jak1 NM_146145 P52332
    Rat Jak1 NM_002227 P23458
    JAK2 Human JAK2 NM_004972 O60674
    Mouse Jak2 NM_008413 Q62120
    Rat Jak2 NM_031514 Q62689
    JAK3 Human JAK3 NM_000215 P52333
    Mouse Jak3 NM_010589 Q62137
    Rat Jak3 NM_012855 Q63272
    Tyk2 Human TYK2 NM_003331 P29597
    Mouse Tyk2 NM_018793 Q9R117
    Rat Tyk2 XM_233741 XP_233741