New therapeutic target with antiresorptive NCE
Dock5 is an activator of the small GTPase Rac essential for bone resorption. Suppression/inhibition of Dock5 affects the organization of cultured osteoclast podosomes into a sealing zone and then prevents bone resorption. Dock5 full KO mice exhibit increased bone mass while they live and breed normally; Dock5 full KO embryos and young mice present normal long bone growth. Systemic administration of selected chemical inhibitor, prevents pathological bone loss in the mouse (menopause, rheumatoid arthritis) without affecting bone formation.
The team has identified 2 chemical series inhibiting human Dock5 activity. Promising results were obtained on mouse and human osteoclasts in culture but also on ovariectomized mice models. Other available data : SAR, early safety (hERG, protein binding…), PK ...
Osteolytic diseases, bone loss
AVAILABLE TECHNOLOGY | Osteolytic diseases – Dock5 – NCE