tcsc2284 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.

IC50 & Target: IC50: 10 nM (JAK1), 28 nM (JAK2), 810 nM (JAK3), 116 nM (Tyk2)

In Vitro: Filgotinib (GLPG0634) dose-dependently inhibits the differentiation of Th2 cells mediated by IL-4, a cytokine that signals through JAK1 and JAK3. Filgotinib also inhibits Th1 differentiation with similar potencies of 1 μM or lower^[1]. Filgotinib (GLPG0634) does not inhibit JAK2 homodimer-mediated signaling induced by EPO or PRL (IC₅₀ > 10 μM)^[2].

In Vivo: Filgotinib (GLPG0634; 3, 10, 30 mg/kg, p.o.) dose-dependently prevents disease progression in the therapeutic rat CIA model. Filgotinib (50 mg/kg, o.p.) protects bone and cartilage from degradation, effectively reduces infiltration of T cells (CD3⁺ cells) and macrophages (F4/80⁺ cells) in the paw, and decreases the serum levels of all cytokines and chemokines measured, including IL-6, IP-10, XCL1, and MCP-1^[1]. Filgotinib (GLPG0634; 0.1 and 0.3 mg/kg) shows efficacy in the rat CIA model^[2].