Baricitinib

As members of the tyrosine kinase family, Janus kinases (JAKs) are intracellular enzymes that modulate signals from cytokines and growth factor receptors involved in hematopoiesis, inflammation, and immune cell function. Upon binding of extracellular cytokines and growth factors, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs). STATs modulate intracellular activity, including gene transcription of inflammatory mediators that promote an autoimmune response, such as IL-2, IL-6, IL-12, IL-15, IL-23, IFN-γ, GM-CSF, and interferons. The JAK-STAT pathway has been implicated in the pathophysiology of rheumatoid arthritis, as it is associated with an overproduction of inflammatory mediators.

There are four JAK proteins: JAK 1, JAK 2, JAK 3 and TYK2. JAKs form homodimers or heterodimers and pair differently in different cell receptors to transmit cytokine signaling. Baricitinib is a selective and reversible inhibitor of JAK1 and JAK2 with less affinity for JAK3 and TYK2; however, the relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known. Baricitinib inhibits the activity of JAK proteins and modulates the signaling pathway of various interleukins, interferons, and growth factors. It was also shown to decrease the proliferation of JAK1/JAK2 expression in mutated cells and induce cell apoptosis.