IL-6 and JAK inhibitors

Question 1

Example of anti-IL6 drig

Answer 1

Tocilizumab

Question 1

Examples of JAK inhibitors

Answer 1

Tofacitinib
Baricitinib

Question 2

How do JAK inhibitors work?

Answer 2

They are associated with receptor tyrosine kinases
- Growth factors or cytokines can signal though the JAK/STAT pathway, through tyrosine kinase receptors
- When GF or cytokines bind, they cause 2 TKR receptors to come together and bind
- The JAKs associated phosphorylate the receptors and attract other proteins e.g. STATs to activate gene transcription of other cytokines
- This increases the inflammatory response

SO by using a JAK inhibitor = JAK protein is inhibited = inhibition of multiple cytokine families = decrease in the inflammatory response

JAK = Janus Kinases

LOOK AT DIAGRAM IN PINK NOTEBOOK

Each cytokine receptor is paired with a different JAK pair, usually as heterodimers. Upon cross-linking by its cytokine, the receptor-associated JAKs transphosphorylate one another. The activated JAKs in turn phosphorylate the cytokine receptor tail. The phosphorylated receptor forms a docking site for STATs, that otherwise reside in the cytosol. These STATs are then phosphorylated by the JAKs before dissociating from the receptor and themselves forming heterodimers or homodimers. They then translocate to the nucleus where they act as transcription factors, regulating gene expression