3-Isoxazolecarboxamide, 5-phenyl-N-[3-(2-thiazolyl)propyl]-

PY-60 is a novel activator of YAP, promoting expansion of epidermal keratinocytes ex vivo and in vivo, targeting ANXA2 to activate YAP, activating a robust, YAP- dependent transcriptional program in multiple cell types. Chemical proteomics revealed the relevant target of PY-60 to be annexin A2 (ANXA2), a protein that directly associates with YAP at the cell membrane in response to increased cell density. PY-60 treatment liberates ANXA2 from the membrane, ultimately promoting a phosphatase-bound, nonphosphorylated and transcriptionally active form of YAP.