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Review
. 2012 Aug;12(4):464-70.
doi: 10.1016/j.coph.2012.06.008. Epub 2012 Jul 19.

Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease

Apostolos Kontzias  1 , Alexander Kotlyar, Arian Laurence, Paul Changelian, John J O'Shea
Affiliations
Review

Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease

Apostolos Kontzias et al. Curr Opin Pharmacol. 2012 Aug.

Abstract

Cytokines are critical for normal cell growth and immunoregulation but also contribute to growth of malignant cells and drive immune-mediated disease. A large subset of immunoregulatory cytokines uses the type I and type II cytokine receptors and pharmacological targeting of these cytokines/cytokines receptors has proven to be efficacious in treating immune and inflammatory diseases. These receptors rely on Janus family of kinases (Jaks) for signal transduction. Recently the first Jak inhibitor (jakinib) has been approved by the FDA and a second has been recommended for approval. Many other Jakinibs are likely to follow and in this brief review, we will discuss the state-of-the art of this new class of pharmacological agents.

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Figures

Figure 1
Figure 1
Jakinibs block multiple aspects of cytokine signaling. Cytokine binding to its cognate receptor leads to phosphorylation of the intracellular domain of the tyrosine kinase receptor by specific Jaks. STATs are then recruited, bind to the receptor and become phosphorylated by Jaks. This results in STAT dimerization, translocation, and regulation of gene transcription. Cytokines also activate the PKB (Akt) and mTOR. Though not carefully studied, it is highly likely that blocking proximal cytokine signals will disrupt all downstream pathways. ** Also referred to as AKT.
Figure 2
Figure 2
Impact of inhibiting various Jaks on signaling by different cytokines
See this image and copyright information in PMC

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