Small molecules induce the TEAD-VGLL4 interaction
TEAD proteins are the main transcriptional effectors of the Hippo signaling pathway and a pharmacological target in oncology. Here, we describe an alternative mechanism for TEAD lipid pocket inhibitors via VGLL4 engagement. We show that specific compounds promote TEAD interaction with the transcriptional repressor VGLL4 to effect global transcript changes, enhance VGLL4 chromatin binding, and suppress cellular proliferation.