Fig. 3.

Identification of small molecules targeting the Hippo-TAZ/YAP pathway. a The Hippo pathway can be regulated at several target points (T1 through T5). The Hippo signaling molecules, MST1/2 (T1) and LATS1/2 (T2), are directly and indirectly affected by compounds such as XMU-MP-1, 9E1, and C19, which affect the activation of TAZ and YAP. YAP and TAZ undergo proteasomal degradation (T3), which is promoted by pazopanib. Nuclear localization of TAZ and YAP (T4) is negatively regulated by statins, dasatinib, pazopanib, and dobutamine, but positively regulated by TM-25659, TM-53/54, and ethacridine. Then YAP/TAZ-TEAD association (T5) is repressed by verteporfin. Pharmacological regulation of the Hippo-TAZ/YAP pathway affects cell proliferation, differentiation, survival, and migration. b Small molecules such as TM-25659 and TM-53/54 promote nuclear localization of TAZ and specifically modulate the association of TAZ with RUNX2, PPARγ, or MyoD and subsequent cell specific gene transcription for bone, adipose, and muscle, respectively