BAY 61-3606 is a cell-permeable, reversible inhibitor of spleen tyrosine kinase (Syk; Ki = 7.5 nM; IC50 = 10 nM). It is 700 to >1,000-fold more selective for Syk over Src, Lyn, Fyn, Itk, and Btk. BAY 61-3606 can inhibit degranulation (IC50 = 5-46 nM) and block cytokine release from mast cells. At 3 mg/kg, oral administration of BAY 61-3606 to rats was shown to suppress antigen-induced passive cutaneous anaphylactic reaction, bronchoconstriction, and bronchial edema. It can also sensitize MCF-7 breast cancer cells to TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis by inhibiting Cdk9. This compound has been used in a pre-clinical model to explore the feasibility of targeting Syk in the treatment of retinoblastoma.
