Information Brigatinib (AP26113) Brigatinib (AP26113) is a potent and selective ALK (IC50, 0.6 nM) and ROS1 (IC50, 0.9 nM) inhibitor. It also inhibits IGF-1R, FLT3, and mutant variants of FLT3 (D835Y) and EGFR with lower potentcy. Targets ALK (Cell-free assay); ROS1 (Cell-free assay); FLT3 (Cell-free assay); IGF1R (Cell-free assay); EGFR(C797S/del19) (cell-based) 16489,0.37 nM; 1.9 nM ;2.1 nM; 24.9 nM; 39.9 nM In vitro Beyond ALK, IGF1R, and InsR, brigatinib also potently inhibits FLT3 and ROS1 with IC50 values of 2.1 and 1.9 nM, respectively. It does not show significant activity toward c-Met or Ron up to 1 μM. Brigatinib overcomes the resistance of EGFR-triple-mutant and the activity depends on ATP-competitive manner with less affection to wild-type EGFR. In vivo Mouse PK parameters for Brigatinib following oral dosing (10 mg/kg): C max =448 ng/mL,t 1/2 =5.8 h. And in CD rats, after dosing at 3 mg/kg i.v, CL=0.46 L/(h·kg), t 1/2 =4.8 h, Vss=7.8 L/kg; Dosed at 10 mg/kg p.o, Cmax=305 ng/mL, t max =4 h, t 1/2 =3.4 h， F%=52. Brigatinib demonstrates dose-dependent antitumor activity. Brigatinib demonstrates growth inhibition activity in PC9 triple-mutant xenograft model and in combination with anti-EGFR antibody to potentiate the efficacy both in vitro and in vivo as shown in first-generation EGFR-TKI-resistant patients. Cell Research(from reference) Cell lines：U937 cells, Karpas-299 cells, H3122 cells Incubation Time：72 h