BIIB-057 is a potent inhibitor of the non-receptor tyrosine kinase Syk (IC50 = 1 nM). It displays at least 80-fold selectivity for Syk over other kinases. BIIB-057 blocks B cell receptor-mediated cell signaling and activation in whole blood (IC50s = 0.27 and 0.28 μM, respectively), as well as Fc? receptor 1-mediated basophil degranulation (IC50 = 0.15 μM). It antagonizes chemokine production, cell migration, and survival of chronic lymphocytic leukemia (CLL) cells after B cell receptor activation and synergistically enhances the action of fludarabine in killing CLL cells. BIIB-057 is orally bioavailable, as it produces dose-dependent anti-inflammatory activity in two rodent models of rheumatoid arthritis. It also prevents splenomegaly and inhibits non-Hodgkin lymphoma tumor growth in a xenograft model.
