TD-198946

TD-198946 is a potent chondrogenic agent. TD-198946 strongly induces chondrogenic differentiation without promoting hypertrophy in cell and metatarsal organ cultures. TD-198946 induces stronger Col2a1 promoter activity than insulin in ATDC5 cells. In C3H10T1/2 cells, ATDC5 cells and primary mouse chondrocytes, TD-198946 dose-dependently stimulates endogenous expression of the chondrocyte markers Col2a1 and Acan , with maximum effects around 1-10 μM.

When administered directly into the joint space, TD-198946 successfully prevents and repaires degeneration of the articular cartilage.It exerts its effect through the regulation of Runx1 expression, which is downregulated in both mouse and human OA cartilage compared with normal tissue.It has disease-modifying effects on progressed osteoarthritis.It may prevent the progression of osteoarthritis by acting on the remaining chondrocytes rather than repairing damaged cartilage, it may be most effective as a therapeutic during the early or middle stages of osteoarthritis, before the articular cartilage is fully eroded. Cartilaginous cell-sheets are generated by culturing mouse and canine costal chondrocytes and human mesenchymal stem cells with TD-198946 on temperature-responsive dishes.