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Overview
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Background
IC50: 5.6 nMRO9021 is a Syk inhibitor.Spleen tyrosine kinase (SYK) is identified as a critical integrator of intracellular signals regulated by activated immunoreceptors, such as Fc receptors and Bcell receptors (BCR), which are of great importantance for the function and development of lymphoid cells.In vitro: Previous study found that in addition to the suppression of Bcell receptor signaling in human peripheral blood mononuclear cells and whole blood, FcγR signaling in human monocytes, and Fc R signaling in human mast cells, RO9021 could also block the in vitro osteoclastogenesis from mouse bone marrow macrophages. Moreover, the Toll-like Receptor 9 signaling in human Bcells could be blocked by RO9021, leading to the decreased levels of plasmablasts, immunoglobulin (Ig) G and IgM upon B-cell differentiation. In addition, RO9021 could also potently inhibit type I interferon production by human plasmacytoid dendritic cells (pDC) via TLR9 activation, and such effect was found to be specific to TLR9 since RO9021 did not show inhibitary effect on TLR4- or JAK-STAT-mediated signaling [1]. In vivo: Animal study showed that the oral administration of RO9021could significanly inhibit the arthritis progression in the mCIA model, with well observed pharmacokinetics-pharmacodynamic correlation [1]. Clinical trial: Up to now, RO9021 is still in the preclinical development stage.
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- Properties
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