A member of the Janus (JAK) family of non-receptor tyrosine kinases, TYK2 plays a critical role in mediating the signaling of the pro-inflammatory p40 subunit-containing cytokines (IL-12 and IL-23) and type 1 interferon. Owing to the high sequence homology within the JAK family catalytic (JH1) domains, achieving high inhibitor selectivity for TYK2 over other Janus family members has proved challenging. The pseudokinase (JH2) domains of the Janus kinases have been shown to regulate function of the JH1 domains in the cellular context, and we’ve shown that functional inhibition of TYK2 is possible via binding to the JH2 domain. The presentation is a high level summary of the story, from start to finish, of how we came to target the pseudokinase as a means to inhibit TYK2 and how we were able to translate this approach to the Phase III agent deucravacitinib.

Inhibition of TYK2 via the pseudokinase: The discovery of deucravacitinib

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.