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Abstract

Brutons Tyrosine Kinase (Btk) Inhibitor Tirabrutinib Suppresses Osteoclastogenesis and Inflammation in a Mouse CollagenInduced Arthritis Model

Rheumatoid arthritis (RA) is characterized by leukocyte infiltration, synoviocyte hyperplasia and osteoclastogenesis, and tyrosine kinases have key roles in the signaling pathways that regulate these processes. Bruton’s tyrosine kinase (Btk) is a key regulator of B-cell receptor (BCR) function. BCR signaling is necessary not only for effective antigen-specific humoral immunity, but for B-cell maturation and survival.

Tirabrutinib is a highly potent and selective Btk inhibitor with an IC50 in the nmol/L range. This study was undertaken to investigate the effect of tirabrutinib on a mouse collagen induced arthritis (CIA) model.

Treatment with tirabrutinib resulted in a dose-dependent inhibition of arthritis severity and bone damage in the CIA model. In a cell-based assay, tirabrutinib prevented the production of inflammatory mediators in monocytes, mast cells and osteoclast.

These data support that tirabrutinib inhibits immune-receptor signaling in multiple cells through Btk inhibition and warrant further clinical testing of tirabrutinib for its therapeutic potential in the treatment of inflammatory diseases.


Author(s): Yuko Ariza, Masayuki Murata, Yoshiko Ueda, Shingo Hotta and Toshio Yoshizawa*

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