| Literature DB >> 25369270 |
Christel J Menet1, Stephen R Fletcher, Guy Van Lommen, Raphael Geney, Javier Blanc, Koen Smits, Nolwenn Jouannigot, Pierre Deprez, Ellen M van der Aar, Philippe Clement-Lacroix, Liên Lepescheux, René Galien, Béatrice Vayssiere, Luc Nelles, Thierry Christophe, Reginald Brys, Muriel Uhring, Fabrice Ciesielski, Luc Van Rompaey.
Abstract
Janus kinases (JAK1, JAK2, JAK3, and TYK2) are involved in the signaling of multiple cytokines important in cellular function. Blockade of the JAK-STAT pathway with a small molecule has been shown to provide therapeutic immunomodulation. Having identified JAK1 as a possible new target for arthritis at Galapagos, the compound library was screened against JAK1, resulting in the identification of a triazolopyridine-based series of inhibitors represented by 3. Optimization within this chemical series led to identification of GLPG0634 (65, filgotinib), a selective JAK1 inhibitor currently in phase 2B development for RA and phase 2A development for Crohn's disease (CD).Entities:
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Year: 2014 PMID： 25369270 DOI： 10.1021/jm501262q
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446