Brigatinib (AP-26113) is a highly potent and selective ALK inhibitor.

IGF-1R:24.9 nM, EGFR (C797S/del19):39.9 nM, FLT3:2.1 nM, ROS1:1.9 nM, ALK:0.37 nM

Beyond ALK, IGF1R, 和 InsR, brigatinib 也强效抑制 FLT3 和 ROS1，其 IC50 值分别为2.1和1.9 nM。对于 c-Met 或 Ron，直到浓度达到1 μM时，brigatinib 未显示出显著活性[1]。Brigatinib 能克服 EGFR 三重突变的耐药性，其活性依赖于 ATP 竞争性方式，对野生型 EGFR 的影响较小[2]。

小鼠口服Brigatinib (10 mg/kg)的药代动力学参数为：Cmax=448 ng/mL，t1/2=5.8小时。CD大鼠经静脉注射3 mg/kg剂量后，清除率(CL)=0.46 L/(h·kg)，t1/2=4.8小时，稳态分布体积(Vss)=7.8 L/kg；口服10 mg/kg剂量后，Cmax=305 ng/mL，tmax=4小时，t1/2=3.4小时，生物利用度(F%)=52。Brigatinib表现出剂量依赖性的抗肿瘤活性[1]。在PC9三重突变异位瘤模型中，Brigatinib表现出生长抑制活性，并且与抗EGFR抗体联合使用，无论是体内还是体外，都能增强对一代EGFR-TKI耐药患者的疗效[2]。

In vitro HotSpotSM kinase profiling of 289 kinases is performed. The assay is conducted in the presence of 10 μM [33P]-ATP, using brigatinib concentrations ranging from 0.05 nM to 1 μM.

All cell lines were used within 20 passages of the initial thaw. Following inhibitor treatment for 72 h, cell growth was assessed to determine the concentration that causes 50% inhibition of cell viability (IC50). (Only for Reference)