VT00278 is a small molecule YAP/TEAD inhibitor, strongly binds to TEAD4 with SPR KD of 3.52 uM, downregulates YAP/TEAD transcriptional activity and potently suppresses tumor-promoting phenotypes including proliferation, invasion and tumor sphere formation.
VT00278 is 10-fold more potent in inhibiting YAP/TEAD reporter activity than its parental compound CA3.
VT00278 greatly down-regulates YAP/TEAD transcriptional activity in the gastric cancer (GC) cell line AGS and GA0518 tumor cells.
VT00278 (200 nM) downregulates genes involved in cell adhesion and cell junctions (both closely linked to the Hippo signaling pathway) in GA0518 cells.
VT00278 exhibits potent antitumor effects and disturbed RNA polymerase II activity, especially inhibiting tumor proliferation, invasion, and cancer stem cell traits.
VT00278 markedly downregulates regulators of RNAPII transcription, impairs cell cycle checkpoints, and strongly induces apoptosis.
VT00278 robustly induces DNA damage, and enhances response to immunotherapy via activating the cytosolic DNA sensing pathway in vivo.
VT00278 exerts strong anti-tumor activity and enhanced the efficacy of immune checkpoint blockade in KP-luc2 syngeneic model.