Drug Discovery – TYK2 (TYrosine Kinase 2)

About TYK2

Tyrosine Kinase 2 (TYK2) controls the JAK-STAT pathway which is over-stimulated in many auto-immune disorders.
The Janus family kinases (JAKs) form a subgroup of non-receptor protein tyrosine kinases which transduce signals from cytokine receptors. TYK2 is a member of the JAK family, which also includes JAK1, JAK2 and JAK3. TYK2 is essential for transducing signals downstream of the IL-12 and IL-23 interleukin receptors, via activation of the transcription factors STAT4 and STAT3. TYK2 may also be important for signalling downstream of the interferon (IFN)-α receptor. These cytokine receptors are involved in pro-inflammatory responses associated with immunological diseases. Thus inhibition of TYK2 has potential for treating diseases such as rheumatoid arthritis, psoriasis and Crohn’s disease.

Small Molecule Inhibitors

Sareum has used its SKIL® platform to develop a novel chemical series that inhibits the activity of TYK2 kinase and is highly selective against the related JAK kinases.

The compounds posses good physicochemical properties and good stability to liver microsomes. The compounds are readily synthesisable and offer excellent scope for further optimisation.

Related compounds within the series show good oral bioavailability (F=90%) and in-vivo T1/2 (>2Hr)

More information about this programme is available here: TYK2 (download pdf)