Filgotinib 是一种选择性的JAK抑制剂，对 JAK1、JAK2、JAK3 和 TYK2 的活性，IC50值分别为 10、28、810 和 116 nM。

GLPG0634(filgotinib) is a selective JAK1 inhibitor. The IC50 values against JAK1, JAK2, JAK3, and TYK2 are 10 nM, 28 nM, 810 nM, and 116 nM, respectively.

对DSS处理小鼠的体内研究显示,Filgotinib (GLPG0634)对JAK1的抑制在临床前小鼠模型中完全可发挥较好的疗效,在发炎的结肠中与STAT3磷酸化的抑制相关.口服给药Filgotinib的绝对生物利用度在大鼠体内适中(45%),而在小鼠体内很高(～100%).在大鼠和小鼠CIA模型中,Filgotinib（30 mg/kg/day,大鼠;50 mg/kg,2次/day,小鼠）可剂量依赖性减少软骨,炎症和骨退化现象.

在细胞系中,GLPG0634抑制IL-2/4诱导的JAK1/JAK3/γc信号和IFN-αB2诱导的JAK1/TYK2 II型受体信号（IC50：150-760 nM）。与JAK/STAT信号中JAK1激酶相比,在细胞水平上GLPG0634对JAK2激酶的选择性更高。此外,GLPG0634也会抑制Th1/2/17细胞的分化。

Recombinant JAK1, TYK2, JAK2, and JAK3 are used to develop activity assays in 50 mM HEPES (pH 7.5), 1 mM EGTA, 10 mM MgCl2, 2 mM DTT, and 0.01% Tween 20. The amount of JAK protein is determined per aliquot, maintaining initial velocity and linearity over time. The ATP concentration is equivalent to 4× the experimental?Km?value and the substrate concentration (ULight-conjugated JAK-1(Tyr1023) peptide) corresponds to the experimentally determined?Km?value. After 90 min incubation at room temperature (RT), the amount of phosphorylated substrate is measured by addition of 2 nM europium-anti-phosphotyrosine Ab and 10 mM EDTA in Lance detection buffer. Compound IC50?values are determined by preincubating the enzyme with compound at RT for 60 min, prior to the addition of ATP.

1206161-97-8

C21H23N5O3S

425.51

GLPG0634

H2O:<1 mgml
Ethanol:<1 mgml
DMSO:79 mg/mL (185.7 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years