Background:

GLPG0634 is a selective inhibitor of JAK1 with IC50 value of 10nM [1].

GLPG0634 is a small molecule inhibitor of JAK1. It shows potent inhibitory activity against both JAK1 and JAK2 with IC50 values of 10nM and 28nM, respectively. In cellular assays, GLPG0634 is most potent in inhibiting the JAK1/JAK3/γc signaling induced by IL-2– and IL-4 as well as the JAK1/TYK2 type II receptor signaling induced by IFN-αB2. However, it shows lower potent to inhibit JAK2 homodimer–mediated signaling induced by EPO or PRL. It demonstrates that GLPG0634 is specific to JAK1. In addition, GLPG0634 is found to inhibit the phosphorylation of STAT1 and STAT5 induced by cytokines. Moreover, GLPG0634 inhibits the differentiation of Th1 and Th2 cells with similar potencies. Th17 differentiation is also affected by GLPG0634 with a lower potency [1].

In the rat model of collagen-induced arthritis (CIA), oral administration of GLPG0634 shows a marked protection from bone damage at dose of 3 mg/kg. It reduces the infiltration of inflammatory cells significantly from 1 mg/kg onward [1].

参考文献:
[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. The Journal of Immunology, 2013, 191(7): 3568-3577.