gp130 inhibitor

Background

Interleukin 6 (IL-6) plays an important role in host defense, but its overexpression leads to the pathogenesis of inflammation, autoimmune diseases and cancer. IL-6 serves as a ligand and activates two membrane-bound glycoprotein receptors, IL-6Rα and gp130.

The binding of IL-6 to IL-6Rα induces trimer formation via recruitment of gp130 followed by formation of hexamer through homodimerization. Then gp130 cytoplasmic domain is phosphorylated by JAKs (JAK1, JAK2, JAK3 or Tyk2), which leads to the activation of STAT3. After phosphorylation, p-STAT3 serves a critical role as a transcription factor.

Concept

In order to block the JAK/STAT signaling through IL-6 receptors, we have planned two approaches, one of which is the blockade of the "intra-trimer" interaction between IL-6 and gp130 by small molecule and the other one is the blockade of the "inter-trimer" interaction of IL-6 and gp130.