BAY-61-3606 BAY-61-3606 is a potent and selective inhibitor of Syk kinase (Ki = 7.5 nM). BAY-61-3606 induces cell cycle arrest and apoptosis .
Targets
Syk (Cell-free assay) 7.5 nM(Ki)
In vitro
BAY 61-3606 is a highly selective inhibitor of Syk kinase. Other selected tyrosine kinases, Lyn, Fyn, Src, Itk, and Btk, are not inhibited by BAY 61-3606 in concentrations up to 4.7 μM. BAY 61-3606 is also found to inhibit B cell receptor (BCR)-mediated signaling. Bay 61-3606 is a sensitizer of TRAIL-induced apoptosis. Mcl-1 downregulation by Bay 61-3606 are concentration- and time-dependent in MCF-7 cells. phosphorylation of Syk is reduced by Bay 61-3606 in MCF-7 and T47D cells. Downregulation of Mcl-1 by Bay 61-3606 is independent of Syk in breast cancer cells. Bay 61-3606 promotes the ubiquitin/proteasome-dependent degradation of the Mcl-1 protein in MCF-7 cells. Bay 61-3606 inhibits the phosphorylation of CDK9, RNA polymerase II, and Mcl-1 expression in MCF-7 cells. Bay 61-3606 inhibits CDK9 kinase activity with an in vitro IC50 of 37 nM.
In vivo
After 20 days of drug administration, the volume of the xenografted tumor was significantly (P <0.001) reduced the efficacy of Bay 61–3606 when administered in TRAIL combination. Oral administration of BAY 61-3606 to rats significantly suppresses antigen-induced passive cutaneous anaphylactic reaction, bronchoconstriction, and bronchial edema at 3 mg/kg. Furthermore, BAY 61-3606 attenuates antigen-induced airway inflammation in rats.
