BIIB-057 is a potent inhibitor of the non-receptor tyrosine kinase Syk (IC50 = 1 nM).1 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 ?M, respectively), as well as Fc? receptor 1-mediated basophil degranulation (IC50 = 0.15 ?M).1 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.2,3 BIIB-057 is orally bioavailable, as it produces dose-dependent anti-inflammatory activity in two rodent models of rheumatoid arthritis.1 It also prevents splenomegaly and inhibits non-Hodgkin lymphoma tumor growth in a xenograft model.3
1.Coffey, G., DeGuzman, F., Inagaki, M., et al.Specific inhibition of spleen tyrosine kinase suppresses leukocyte immune function and inflammation in animal models of rheumatoid arthritisJ. Pharmacol. Exp. Ther.340(2)350-359(2012) 2.Hoellenriegel, J., Coffey, G.P., Sinha, U., et al.Selective, novel spleen tyrosine kinase (Syk) inhibitors suppress chronic lymphocytic leukemia B-cell activation and migrationLeukemia26(7)1576-1583(2012) 3.Spurgeon, S.E., Coffey, G., Fletcher, L.B., et al.The selective Syk inhibitor P505-15 (PRT062607) inhibits B cell signaling and function in vitro and in vivo and augments the activity of fludarabine in chronic lymphocytic leukemiaJ. Pharmacol. Exp. Ther.344(2)378-387(2015)