MSC-4106

MSC-4106 is an orally active small molecule inhibitor of the YAP/TAZ-TEAD protein-protein interaction, developed by Merck KGaA. It specifically targets TEAD transcription factors, including TEAD1 and TEAD3, by binding to the palmitate-binding pocket (P-site). This binding blocks the auto-palmitoylation of TEAD proteins, which is essential for their stability and interaction with YAP/TAZ co-activators, thereby disrupting the Hippo signaling pathway. MSC-4106 has demonstrated preclinical efficacy in mesothelioma models (e.g., NCI-H226) and served as a lead compound for the development of the more potent, TEAD1-selective clinical candidate M3686.