QL-1200186

Description

QL-1200186 is a selective, orally active, allosteric inhibitor targeting the tyrosine kinase TYK2 pseudokinase domain JH2 IC50=0.06 nM, TYK2 JH2 , with 164-fold selectivity over TYK1 JH2 IC50=9.85 nM?TYK1 JH2 . QL-1200186 first stabilizes the TYK2 JH2 conformation, inhibits the activity of the JH1 catalytic domain, and blocks the IFN?, IL-12/IL-23-mediated JAK-STAT signaling pathway. QL-1200186 can inhibit the production of Th1/Th17 cell-related cytokines such as IFN?, IL-23 , reduce immune cell activation, and has no significant effect on JAK1/2/3 kinase activity. QL-1200186 can significantly improve skin inflammation in the Imiquimod HY-B0180 -induced psoriasis mouse model and reduce the Psoriasis Area and Severity Index PASI score. QL-1200186 can be used in the study of autoimmune diseases such as psoriasis and systemic lupus erythematosus SLE .