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

METHODS: Transepithelial drug transport was assessed using polarized monolayers of MDCK-II parental cells and their subclones overexpressing hABCB1, hABCG2, or mAbcg2 treated with Fisogatinib (BLU-554) (5 μM).
RESULTS Fisogatinib (BLU-554) was moderately transported by hABCB1 and slightly transported by mAbcg2. [4]

METHODS: A preliminary experiment was conducted in which male wild-type and Oatp1a/1b−/− mice were given Fisogatinib (BLU-554) (10 mg/kg, oral) and the plasma concentration before 4 hours and the liver-to-plasma ratio at 4 hours were analyzed.
RESULTS Oatp1a/1b protein had little effect on the oral efficacy or liver distribution of Fisogatinib (BLU-554) in mice. [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].