TM-25659 is a modulator of transcriptional co-activator with PDZ-binding motif (TAZ), with anti-osteoporotic and anti-obesity activities.

Treatment with TM-25659 (2, 10, 20, 100 μM) dose-dependently enhances nuclear TAZ localization and attenuates PPARγ-mediated adipocyte differentiation by facilitating PPARγ suppression activity of TAZ. Osteogenic gene expression is enhanced by TM-25659 (2, 10, 50 μM) and thereby osteoblast differentiation is increased[1].

In vivo, TM-25659 (50 mg/kg, i.p., every other day for 2 weeks) suppresses bone loss and decreases weight gain in an obesity model. The plasma concentration of TM-25659 declines with an approximate t1/2 of 7 or 10 h following i.v or p.o. administration respectively. The systemic clearance (CL) is 0.21 L/(h×kg) and the volume of distribution at steady-state (1.91 L/(h×kg)) is larger than the volume of total body fluids[1].