Janus kinases: an ideal target for the treatment of autoimmune diseases

Abstract

Cytokines have pivotal roles in the maintenance of an appropriate immune response. Targeting cytokine receptors has been an effective means of treating immune-related disorders. In the past few years, research efforts have been directed toward cytokines' intracellular signaling pathways and, in particular, the JAK-STAT (Janus kinase-signal transducers and activation of transcription) signaling cascade. Recently, spearheaded by the development of effective drugs in cancer treatment, it has become clear that the targeting of intracellular protein kinases is a very attractive and feasible possibility for the treatment of autoimmune disorders. The targeting of the Janus kinases (JAKs) has been quite successful and two JAK inhibitors are now approved to be used in humans. Interestingly, although some of the inhibitors developed and tested to date have been shown to target more than one kinase, this promiscuity does not appear to be problematic. Novel second-generation, more specific inhibitors are under development, and in the next few years, we expect this class of drugs to become a powerful tool in the hands of clinician treating autoimmune diseases.

FIGURE 1. JAK inhibitors blok JAKs enzymatic activity activation

Cytokines or interferons bind their cognate receptors and initiate a signaling cascade leading to activation of the latent transcription factors STAT and ultimately gene transcription. JAK inhibitors interfere with this pathway by blocking JAKs enzymatic activity.