PF-06726304

PF-06726304 is a small molecule inhibitor of the Polycomb Repressive Complex 2 (PRC2), specifically targeting the catalytic subunit Enhancer of Zeste Homolog 2 (EZH2) and the regulatory subunit Embryonic Ectoderm Development (EED). Developed by Pfizer, it is primarily investigated for its activity against malignant melanoma. Unlike traditional EZH2 inhibitors that primarily block histone H3K27 trimethylation, PF-06726304 has been observed to markedly reduce the protein levels of EED and EZH2 without significantly altering total H3K27me3 levels in certain cell lines. Its anti-tumor mechanism is also linked to the modulation of the Akt-EZH2 signaling axis, characterized by reduced phosphorylation of Akt (Ser473) and EZH2 (Ser21).