BAY 61-3606 dihydrochloride (BAY 61-3606) is a potent and selective inhibitor of Syk kinase (Ki = 7.5 nM).

Syk:7.5 nM(Ki)

BAY 61-3606 是一种高度选择性的 Syk 激酶抑制剂。其对其他被选择的酪氨酸激酶，如 Lyn, Fyn, Src, Itk 和 Btk 在高达 4.7 μM 的浓度下不表现出抑制作用。此外，BAY 61-3606 还能抑制 B 细胞受体（BCR）介导的信号传导[1]。Bay 61-3606 增强 TRAIL 诱导的凋亡，它对 Mcl-1 的降级在 MCF-7 细胞中是浓度和时间依赖的。Bay 61-3606 在 MCF-7 和 T47D 细胞中减少 Syk 的磷酸化。Bay 61-3606 在乳腺癌细胞中降低 Mcl-1 的作用与 Syk 无关。Bay 61-3606 促进 MCF-7 细胞中 Mcl-1 蛋白的泛素/蛋白酶体依赖性降解。Bay 61-3606 抑制 MCF-7 细胞中 CDK9、RNA 聚合酶 II 和 Mcl-1 表达的磷酸化。Bay 61-3606 以 37 nM 的体外 IC50 抑制 CDK9 激酶活性[2]。

经过20天的化合物给药后，异种移植瘤的体积显著减少（P <0.001），显示了在TRAIL组合[2]中给予BAY 61-3606的有效性。口服BAY 61-3606至大鼠，在3 mg/kg的剂量下，显著抑制抗原诱导的被动皮肤过敏反应、支气管收缩及支气管水肿。此外，BAY 61-3606还减轻了大鼠抗原诱导的气道炎症[1]。

GST-Syk (3.2?ng), 0.5?μg AL, 30?μM ATP, and testing compound in the presence of 0.25% Me2SO are mixed in 50?μL/well of kinase assay buffer in polypropylene U-bottom 96-well microtiter plates. The mixture is incubated for 1?h at room temperature, and the reaction is terminated by the addition of 120?μL of termination buffer. To capture AL, 120?μL of the terminated mixture is transferred to streptavidin-coated plates, followed by incubation at room temperature for more than 30?min. After three ishes with washing buffer, 100?μL of antibody buffer is added and incubated at room temperature for more than 30?min. After three more ishes, 100?μL of enhancement solution is added. Time-resolved fluorescence is measured by multilabel counter ARVO.

MCF-7 cells are exposed to TRAIL (indicated concentrations:0, 12.5, 25, 37.5 ng/ml) with or without Bay 61-3606 (2.5 μM) for 24 h; After exposure to the agents for 12 h, MCF-7 cells are subjected to immunocytochemistry using an active Bak antibody; Caspase activity is measured in MCF-7 cells exposed to Bay 61-3606 (5 μM) with or without TRAIL (50 ng/ml) for 24 h.(Only for Reference)