Brigatinib (C09-0785-856)

InformationBrigatinib (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.TargetsALK (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 nMIn vitroBeyond 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 vivoMouse PK parameters for Brigatinib following oral dosing (10 mg/kg): Cmax=448 ng/mL,t1/2=5.8 h. And in CD rats, after dosing at 3 mg/kg i.v, CL=0.46 L/(h·kg), t1/2=4.8 h, Vss=7.8 L/kg; Dosed at 10 mg/kg p.o, Cmax=305 ng/mL, tmax=4 h, t1/2=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. Specification: 0.98 Molecular Formula: C29H39ClN7O2P Molecular Weight: 584.09 PubChem CID: 68165256 Isomeric SMILES: CN1CCN(CC1)C2CCN(CC2)C3=CC(=C(C=C3)NC4=NC=C(C(=N4)NC5=CC=CC=C5P(=O)(C)C)Cl)OC Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/B413950-SCI_d0dbc6830b198cbca3e9c2dd16af2cba.pdf