Brigatinib 是一种有效，选择性的ALK抑制剂 (IC50:0.6 nM)。

Brigatinib is a highly potent and selective ALK inhibitor.

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[1]. Brigatinib overcomes the resistance of EGFR-triple-mutant and the activity depends on ATP-competitive manner with less affection to wild-type EGFR[2].

Mouse 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[1]. 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[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)

1197953-54-0

C29H39ClN7O2P

584.1

AP-26113;布格替尼

H2O:Insoluble
DMSO:Insoluble
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In solvent: -80°C for 2 years