Background:

EPZ005687 is a potent inhibitor of EZH2, an enzymatic subunit of polycomb repressive complex 2 (PRC2) catalyzing the methylation of histone H3 lysine 27 (H3K27), that inhibits EZH2 with a value of inhibition constantK_iof 24 nM, which is 500-fold and 50-fold greater in selectivity than 15 other protein methyltransferases and closely related EZH1 respectively. EPZ005687 concentration-dependently inhibits the enzymatic activity of PRC2 with a value of 50% inhibition concentration IC₅₀of 54 nM through binding to the S-adenosylmethionine (SAM) pocket of the EZH2 SET domain. Study results have shown that EPZ005687 reduces H3K27 methylation in a variety of lymphoma cells and induces apoptotic cell killing in heterozygous Tyr641 or Ala677 mutant cells.

Reference

?[1].Knutson SK, Wigle TJ, Warholic NM, Sneeringer CJ, Allain CJ, Klaus CR, Sacks JD, Raimondi A, Majer CR, Song J, Scott MP, Jin L, Smith JJ, Olhava EJ, Chesworth R, Moyer MP, Richon VM, Copeland RA, Keilhack H, Pollock RM, Kuntz KW. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol. 2012 Nov;8(11):890-6.