PFI-2 ((R)-PFI-2) is a first-in-class, potent and selective inhibitor of SETD7 methyltransferase with Ki app/IC50 of 0.33/2 nM, respectively.
PFI-2 shows high selectivity (>1,000-fold) for SETD7 over 18 other methyltransferases and DNMT1, 500-fold more active than enantiomer (S)-PFI-2.
PFI-2 increases YAP nuclear localization, regulates YAP target genes, and phenocopys the effects of Setd7 deficiency on Hippo pathway signaling in murine embryonic fibroblasts.
