Janus Kinase (JAK)-inhibitors

Introduction

Janus Kinase (JAK) inhibitors are a class of drugs that target the Janus Kinase family of enzymes. Janus Kinases are a family of cytoplasmic tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway.

The Janus Kinases are:

• JAK1
• JAK2
• JAK3
• TYK2

Janus kinase inhibitors can be classed in several overlapping classes: they are immunomodulators, they are DMARDs (disease-modifying antirheumatic drugs), and they are a subclass of tyrosine kinase inhibitors.

Mechanism of action

JAK-inhibitors work by modifying the immune system via cytokine activity inhibition. The JAK enzymes interact with the intracellular part of distinct cytokine receptors, and are thus involved in the signaling pathways of multiple pro-inflammatory cytokines, such as IL-2, 4, 7, 9, 13, 15, 17, 21, 23. By inhibiting JAK enzymes, JAK inhibitors can modulate the immune response and reduce inflammation. JAK inhibitors are used to treat a variety of autoimmune and inflammatory diseases, including rheumatoid arthritis, psoriasis, and inflammatory bowel disease.

Examples of JAK inhibitors

First generation JAK inhibitors:

• Tofacitinib (JAK1/3 inhibitor)
• Ruxolitinib (JAK1/2 inhibitor)

Second generation JAK inhibitors:

• Upadacitinib (selective for JAK1)