ATC Group: L04AF Janus-associated kinase (JAK) inhibitors

Baricitinib is a selective and reversible inhibitor of Janus kinase (JAK)1 and JAK2. In isolated enzyme assays, baricitinib inhibited the activities of JAK1, JAK2, Tyrosine Kinase 2 and JAK3 with IC₅₀ values of 5.9, 5.7, 53 and >400 nM, respectively. Janus kinases (JAKs) are enzymes that transduce intracellular signals from cell surface receptors for a number of cytokines and growth factors involved in haematopoiesis, inflammation and immune function.

Deucravacitinib selectively inhibits the TYK2 enzyme (TYK2 belongs to the JAK family). TYK2 mediates signalling of interleukin-23 (IL-23), interleukin-12 (IL-12), and type I interferons (IFN), which are naturally occurring cytokines involved in inflammatory and immune responses. Deucravacitinib inhibits the release of proinflammatory cytokines and chemokines.

Filgotinib is an adenosine triphosphate (ATP)-competitive and reversible inhibitor of the JAK family. Within the signalling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs) which modulate intracellular activity including gene expression. Filgotinib modulates these signalling pathways by preventing the phosphorylation and activation of STATs. Filgotinib is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients.

Ritlecitinib irreversibly and selectively inhibits Janus kinase (JAK) 3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) family by blocking the adenosine triphosphate (ATP) binding site. JAK3 and TEC family mediated signalling pathways are both involved in alopecia areata pathogenesis, although complete pathophysiology is still not understood.

Tofacitinib is a potent, selective inhibitor of the JAK family. In human cells, tofacitinib preferentially inhibits signalling by heterodimeric cytokine receptors that associate with JAK3 and/or JAK1. Inhibition of JAK1 and JAK3 by tofacitinib attenuates signalling of interleukins and type I and type II interferons, which will result in modulation of the immune and inflammatory response.

Upadacitinib is a selective and reversible Janus kinase (JAK) inhibitor. In human cellular assays, upadacitinib preferentially inhibits signalling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2. JAK1 is important in inflammatory cytokine signals while JAK2 is important for red blood cell maturation and JAK3 signals play a role in immune surveillance and lymphocyte function.