PFI-2

PFI-2 is a highly potent and selective small-molecule inhibitor of the histone methyltransferase SET domain containing 7 (SETD7), also known as SET7/9. Developed as a chemical probe by Pfizer in collaboration with the Structural Genomics Consortium (SGC), PFI-2 binds to the substrate-binding site of SETD7 in a substrate-competitive manner, effectively blocking its methyltransferase activity. Research has demonstrated its potential in various disease models, including Autosomal Dominant Polycystic Kidney Disease (ADPKD), where it inhibits cystogenesis by modulating the PKA-SETD7-PKA feedback loop, and obesity-related heart failure with preserved ejection fraction (HFpEF), where it reduces myocardial inflammation and cardiomyocyte stiffness by preventing SETD7-mediated H3K4 methylation on inflammatory gene promoters like NF-kB p65.

Other names

(R)-PFI-2SETD7 inhibitor PFI-2SETD-7 inhibitor PFI-2SETD 7 inhibitor PFI-2