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Inhibition of JAK/STAT signalling pathway in rheumatoid synovial fibroblasts using small molecule compounds

Migita K, Izumi Y, Torigoshi T et al. - Clin Exp Immunol. 2013 Aug 23. doi: 10.1111/cei.12190

Current JAK inhibitors CP-690,550 and INCB020850 have inhibitory effects on multiple JAK pathways, therefore Migita et al. tested whether selective inhibition of JAK3, using PF-956980, would be enough to ameliorate the rheumatoid inflammatory process. The results indicated that the inhibition of JAK3 alone is does not achieve control of STAT3-dependent signalling, and while it is suggested that the targeting of singular JAK pathways should lead to fewer adverse events, it appears that this approach does not reach the desired level of disease control. Therefore the authors conclude that inhibition of JAK3 alone is not sufficient and that inhibiting JAK 1/2 is needed to control the pro-inflammatory cascades of the disease.

Keywords: JAK, Preclinical, MOA

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Upload date: October 2013

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