MRK-A

MRK-A is a novel, potent, and selective small molecule inhibitor of the YAP1/TAZ-TEAD transcriptional complex, developed by Merck. It belongs to an aryl ether chemical series and functions by allosterically binding to the hydrophobic palmitate pocket of TEAD proteins (specifically TEAD1 and TEAD2), thereby disrupting the interaction between YAP1/TAZ and TEAD transcription factors. This inhibition suppresses the expression of pro-survival and pro-proliferative target genes such as CYR61, ERBB3, ANKRD1, and CTGF. MRK-A has demonstrated significant anti-tumor activity in NF2-deficient mesothelioma models and is being investigated for the treatment of malignancies driven by dysregulated Hippo pathway signaling.