GLPG0634

Uses

N-[5-[4-[(6-Cyano-3-pyridinyl)methoxy]phenyl][1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide, is an orally-available, selective inhibitor of JAK1 (Janus kinase 1), used for the treatment of rheumatoid arthritis and potentially other inflammatory diseases.

Biological Activity

glpg0634 is a potent and selective inhibitor of jak1 with ic50 values of 10, 28, 810 and 116 nm for jak1, jak2, jak3 and tyk2, respectively [1].janus kinase 1 (jak1) is a member of the jak family and is a non-receptor tyrosine kinase. jaks play an important role in the immune system. jak1 is a potential target for the treatment of immune-inflammatory diseases [1].glpg0634 is a potent and selective jak1 inhibitor. glpg0634 inhibited jak1, jak2, jak3 and tyk2 with ic50 values of 10, 28, 810 and 116 nm, respectively. in cd4+ t cells, glpg0634 significantly reduced il-6-induced stat1 phosphorylation with ic50 value of 629 nm, which suggested the inhibition of jak1. in cd33+ t cells, glpg0634 reduced gm-csf-induced stat5 phosphorylation with ic50 value of 17.5 μm, suggesting the inhibition of jak2. glpg0634 inhibited the differentiation of th1 and th2 cells mediated by il-4 and il-12, respectively. also, glpg0634 inhibited th17 differentiation induced by tgf-β, il-23, il-6 and il-1β [1].in rats, glpg0634 significantly reduced the mrna levels of mx2, which were modulated by ifn-α-jak1/tyk2 signaling. in collagen-induced arthritis (cia) rat model, glpg0634 significantly reduced the infiltration of inflammatory cells and reduced the levels of il-6, ip-10, xcl1 and mcp-1 [1].

target

JAK1

References

[1]. van rompaey l, galien r, van der aar em, et al. preclinical characterization of glpg0634, a selective inhibitor of jak1, for the treatment of inflammatory diseases. j immunol, 2013, 191(7): 3568-3577.