Filgotinib-d4

Filgotinib-d₄ is intended for use as an internal standard for the quantification of filgotinib by GC- or LC-MS. Filgotinib is a JAK1 inhibitor (IC₅₀ = 10 nM).¹ It is selective for JAK1 over JAK3 (IC₅₀ = 810 nM) but also inhibits JAK2 and tyrosine kinase 2 (Tyk2; IC₅₀s = 28 and 116 nM, respectively), as well as Abl, FLT1, -3 and -4, FMS, Mer, and TBK1 activity by greater than 35% in a panel of 177 tyrosine kinases at 1 μM. Filgotinib inhibits IL-6-induced phosphorylation of STAT1 in CD4⁺ T cells with an IC₅₀ value of 629 nM in isolated human whole blood. It reduces hind paw macrophage and T cell infiltration and bone erosion in a rat model of collagen-induced arthritis when administered at doses ranging from 0.1 to 30 mg/kg per day for 15 days.

Filgotinib-d4 is the deuterium labeled Filgotinib. Filgotinib (GLPG0634) is a selective JAK1 inhibitor with IC50 of 10 nM, 28 nM, 810 nM, and 116 nM for JAK1, JAK2, JAK3, and TYK2, respectively.

1. Van Rompaey, L., Galien, R., van der Aar, E.M., et al. Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases J. Immunol. 191(7),3568-3577(2013).