MGH-CP1

MGH-CP1 is a potent and selective **small molecule inhibitor** of TEAD (Transcriptional Enhanced Associate Domain) palmitoylation, specifically targeting TEAD2 and TEAD4 auto-palmitoylation with IC50 values of 710 nM and 672 nM, respectively. By blocking palmitoylation, MGH-CP1 suppresses activation of the TEAD–YAP/TAZ transcriptional complex, which regulates gene expression involved in cancer cell stemness, migration, YAP-dependent organ overgrowth, and tumor initiation. It shows high selectivity for TEAD palmitoylation, without affecting ZDHHC-family palmitoyl acyltransferases. In preclinical studies, MGH-CP1 was shown to inhibit YAP/TAZ-mediated transcription and reduce tumor growth and organ overgrowth in vivo, including in hepatic and uveal melanoma models. It is well-tolerated in animals and does not induce cell death but causes a proliferation stasis in YAP-dependent tumors. Developed as a tool compound for Hippo signaling-related cancer biology, it is distinguished as the first inhibitor of the TEAD palmitate-binding pocket[1][2][3][4][5][6].