Fisogatinib 是高效的、选择性的、口服具有活力的 FGFR4 抑制剂 (IC50:5 nM)。它在依赖FGFR4信号传导的肝细胞癌模型中具有显著的抗肿瘤活性。

BLU-554 is a potent inhibitor of fibroblast growth factor receptor 4 (FGFR4).

BLU-554 exploits a unique interaction with FGFR4 to confer potency and selectivity

BLU-554 is well tolerated in these tumor models. Administration of BLU-554 induces tumor regression in liver cancer models[1].

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].

1707289-21-1

C24H24Cl2N4O4

503.38

BLU554;BLU-554;BLU 554

Ethanol:2 mg/mL (3.97 mM)
DMSO:93 mg/mL (184.8 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years