RO9021

RO9021 potently inhibits SYK kinase activity with an average IC50 of 5.6 nM and suppresses B-cell receptor signaling.

RO9021 suppresses BCR signaling in human peripheral blood mononuclear cells (PBMC) and whole blood, FcR signaling in human monocytes, and FcR signaling in human mast cells and blocks osteoclastogenesis from mouse bone marrow macrophages in vitro. Toll-like Receptor(TLR) 9 signaling in human Bcells was inhibited by RO9021, resulting in decreased levels of plasmablasts, immunoglobulin (Ig)M and IgG upon B-cell differentiation. RO9021 also potently inhibited type I interferon production by human plasmacytoid dendritic cells (pDC) upon TLR9 activation. This effect is specific to TLR9 as RO9021 did not inhibit TLR4- or JAK-STAT-mediated signaling. RO9021 does not appreciably inhibit the JAK-STAT pathway.