Lorecivivint (SM04690), a Potential Disease-Modifying Osteoarthritis Drug, Inhibits CLK2 and DYRK1A, Novel Molecular Regulators of Wnt Signaling, Chondrogenesis, and Inflammation

Background: In the synovial joint, upregulated Wnt signaling affects osteoarthritis (OA) pathogenesis by increasing inflammation and subchondral bone formation as well as thinning cartilage. A novel small molecule, lorecivivint (LOR; SM04690), was previously shown to exhibit OA disease-modifying properties through Wnt pathway inhibition in vitro and in vivo. Herein, we describe the novel mechanism of action of LOR affecting Wnt pathway inhibition, chondrocyte differentiation, and anti-inflammatory activity.