2. Academic Validation
  3. Triazolopyridines as selective JAK1 inhibitors: from hit identification to GLPG0634

Triazolopyridines as selective JAK1 inhibitors: from hit identification to GLPG0634

  • J Med Chem. 2014 Nov 26;57(22):9323-42. doi: 10.1021/jm501262q.
Christel J Menet 1,  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
Affiliations

Affiliation

  • 1 Galapagos NV , Generaal de Wittelaan L11A3, 2800 Mechelen, Belgium.
PMID: 25369270 DOI: 10.1021/jm501262q
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).

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