Lanraplenib (GS-9876) is a highly selective and orally active SYK inhibitor (IC50=9.5 nM) in development for the treatment of inflammatory diseases. Lanraplenib inhibits SYK activity in platelets via the glycoprotein VI (GPVI) receptor without prolonging bleeding time (BT) in monkeys or humans.

Syk:9.5 nM

Lanraplenib (GS-9876) inhibits glycoprotein VI (GPVI)-induced phosphorylation of linker for activation of T cells and phospholipase Cγ2, platelet activation and aggregation in human whole blood, and platelet binding to collagen under arterial flow [2]. Lanraplenib inhibits anti-IgM stimulated phosphorylation of AKT, BLNK, BTK, ERK, MEK, and PKCδ in human B cells (EC50s: 24-51 nM). Lanraplenib inhibits anti-IgM mediated CD69 and CD86 expression on B-cells (EC50: 112±10 nM and 164±15 nM, respectively) and anti-IgM /anti-CD40 co-stimulated B cell proliferation (EC50: 108±55 nM). In human macrophages, Lanraplenib inhibits IC-stimulated TNFα and IL-1β release (EC50: 121±77 nM and 9±17 nM, respectively) [1].