YAP activator PY-60 (PY-60) is a novel small molecule activator of YAP transcriptional activity (EC50=1.5 uM) via targeting annexin A2 (ANXA2).
PY-60 dose-dependently induced luciferase activity in 293A-TEAD-LUC cells, robustly activateed YAP transcriptional activity in vitro.
PY-60 treatment robustly increased the levels of YAP-controlled transcripts (ANRKD1, CYR61 and CTGF) in 293A cells and other human cell lines (MCF10A, HEK293T, H69 and HaCaT), but did not augment the levels of YAP itself (YAP1).
PY-60 promotes YAP-dependent expansion of epidermal keratinocytes in mouse following topical drug administration. Annexin A2 (ANXA2) is 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.
