Discovery of GLPG1972/S201086, a Potent, Selective, and Orally Bioavailable ADAMTS-5 Inhibitor for the Treatment of Osteoarthritis
F. Brebion, Romain Gosmini, Pierre Deprez, Marie Varin, Christophe Peixoto, Luke J. Alvey, Hélène Jary, Natacha Bienvenu, Nicolas Triballeau, Roland Blanqué, C. Cottereaux, Thierry Christophe, Nele Vandervoort, Patrick Mollat, Robert Touitou, Philip M. Leonard, Frédéric De Ceuninck, Iuliana Botez, Alain Monjardet, Ellen van der Aar, David Amantini
Abstract
< 1.5 μM). The cocrystal structure of GLPG1972/S201086 with human recombinant ADAMTS-5 is discussed. GLPG1972/S201086 has been investigated in a phase 2 clinical study in patients with knee OA (NCT03595618).
Topics & Concepts
ADAMTSAggrecanaseChemistryOsteoarthritisAggrecanCartilagePharmacologyDrug discoveryBiochemistryMatrix metalloproteinaseMetalloproteinaseThrombospondinMedicineArticular cartilagePathologyAlternative medicineAnatomyOsteoarthritis Treatment and MechanismsInflammatory mediators and NSAID effectsComputational Drug Discovery Methods