Pharmacological regulators of Hippo pathway: Advances and challenges of drug development

The Hippo signaling pathway is crucial in regulating organ size, tumor progression, tissue regeneration, and bone homeostasis. Inactivation of the Hippo pathway results in the nuclear translocation and activation of YAP/TAZ. This activation not only promotes tumor progression but also enhances tissue regeneration, wound healing, and maintenance of bone stability Although its discovery occurred over two decades ago, developing effective inhibitors or activators for the Hippo pathway remains challenging. Recently, however, the pace of advancements in developing Hippo signaling-related agonists and antagonists has accelerated, with some drugs that target TEAD advancing to clinical trials and showing promise for treating related diseases. This review summarizes the progress in research on Hippo signaling-related agonists and inhibitors, offering an in-depth analysis of their regulatory mechanisms, pharmacological properties, and potential in vivo applications.