PY-60

PY-60 is a small molecule activator of the Yes-associated protein (YAP), a primary effector of the Hippo signaling pathway. It functions by directly binding to Annexin A2 (ANXA2), which facilitates the nuclear translocation and transcriptional activity of YAP. In the context of endothelial biology, PY-60 has been shown to preserve the alveolar-capillary barrier and attenuate lung injury induced by pathogens such as Methicillin-resistant Staphylococcus aureus (MRSA). By promoting YAP signaling, the compound helps maintain the levels of key junctional proteins like VE-cadherin, thereby reducing vascular permeability and pulmonary edema. While currently utilized primarily as a research tool to investigate tissue regeneration and endothelial responses, its mechanism of action suggests potential therapeutic utility in treating acute respiratory distress syndrome (ARDS) and other conditions characterized by barrier dysfunction.