Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 Inhibitors.

ABSTRACT:

Introduction

Deucravacitinib, a novel, oral, selective inhibitor of tyrosine kinase 2 (TYK2) signaling, acts via an allosteric mechanism by binding to the enzyme's regulatory domain instead of the catalytic domain. This unique binding provides high functional selectivity for TYK2 versus the closely related Janus kinases (JAKs) 1/2/3. Deucravacitinib was efficacious in phase 2 and 3 psoriasis trials, without clinical or laboratory parameters indicative of JAK 1/2/3 inhibition being observed. This analysis compared the kinase specificities of deucravacitinib versus JAK 1/2/3 inhibitors at therapeutic exposures.

Methods

Signaling via JAK 1/3, JAK 2/2, and TYK2/JAK 2 dimers was measured in in vitro whole blood assays. Concentrations providing half-maximal inhibition (IC_50</

SUBMITTER: Chimalakonda A 

PROVIDER: S-EPMC8484413 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature