Janus kinase 1 (JAK1) (JAK1)

Janus kinase 1 (JAK1) is a non-receptor tyrosine kinase that serves as a critical mediator in the JAK-STAT signaling pathway, which is essential for the intracellular transmission of signals from various cytokines and growth factors [1, 14]. It associates with type I and type II cytokine receptors, including those for the IL-2, IL-4, IL-6, and IL-10 families, as well as interferons, to regulate immune responses, cell proliferation, and hematopoiesis [6, 17, 20]. Dysregulation or overactivation of JAK1 is strongly linked to inflammatory and autoimmune diseases, such as atopic dermatitis and rheumatoid arthritis, and it also plays a role in the progression of certain cancers [7, 11, 19]. Therapeutic agents like abrocitinib are designed to selectively inhibit JAK1 by competitively binding to its ATP-binding site, thereby preventing the phosphorylation of Signal Transducers and Activators of Transcription (STAT) proteins [3, 5]. This inhibition effectively blocks the downstream expression of pro-inflammatory genes, leading to reduced clinical symptoms such as pruritus and skin inflammation [2, 4]. However, because JAK1 is involved in broad immune surveillance, its inhibition is associated with safety concerns including serious infections, herpes zoster reactivation, and potential risks for malignancy or cardiovascular events [12, 16, 18].

Other names

JAK1AJAK1BJTK3Tyrosine-protein kinase JAK1

Selective, reversible inhibition of JAK1 kinase activity, which prevents the phosphorylation and activation of STAT proteins, thereby blocking the JAK-STAT signaling pathway and the transcription of pro-inflammatory cytokines.