Fisogatinib (BLU-554) is a highly potent, selective and orally active FGFR4 inhibitor with an IC50 value of 5 nM and significant anti-tumor activity in hepatocellular carcinoma models dependent on FGFR4 signaling.

FGFR4:5 nM

方法：使用Fisogatinib (BLU-554) （5μM）处理利用MDCK-II亲本细胞及其过表达hABCB1、hABCG2或mAbcg2的亚克隆的极化单层来评估经上皮药物转运。
结果：Fisogatinib (BLU-554) 被hABCB1适度转运，被mAbcg2轻微转运。[4]

方法：对雄性野生型和Oatp1a/1b−/−小鼠给予Fisogatinib (BLU-554) (10mg/kg, 口服）进行了初步实验，并分析了4h前的血浆浓度和4h时肝脏与血浆的比率。
结果：Oatp1a/1b蛋白对Fisogatinib (BLU-554)口服有效性或小鼠肝脏分布的影响很小。[4]

The Ki value and mode of inhibition of LY2801653 for the MET kinase activity are determined using a radiometric filter-binding assay. Reactions are carried out in 96-well plates in Enzyme dilution buffer (EDB) compose of 50 mM Tris HCl pH 7.5, 2 mM DTT, 0.005% Triton X-100, 10 mM MgCl2, and 250 ?M EDTA. Serially diluted LY2801653 (final concentration 250 to 0 nM) are followed by the addition of a series of 8 concentrations of 33P-γ-ATP (final concentration 400 to 10 μM ATP), and 5 nM enzyme (final concentration). After a 2-hour incubation, PolyGluTyr synthetic protein substrate (final 150 μg/mL) is added to initiate the 30-minute kinase reaction. Reactions are quenched with 10% H3PO4, transfer to a pre-wetted Multiscreen anionic phosphocellulose 96-well filter plate, and washed; radioactivity is measured with a scintillation counter. The experimental data are fit to a global mix model inhibition equation using GraphPad Prism softwar to generate an alpha value to determine the modality of inhibition and to calculate the Ki value for LY2801653[1].