cpi-360

Description: CPI-360 is a novel, highly potent, selective, and SAM-competitive inhibitor of enhancer of zeste homolog 2 (EZH2) with potential antitumor activity. It inhibits wt EZH2 and Y641N EZH2 with an IC50 of 0.5 nM and 2.5 nM, respectively. CPI-360 exhibits excellent antiproliferative activity and high in vivo antitumor efficacy. It functions on the basis of S-adenosyl-Lmethionine (SAM)-competition, inhibits EZH1 about 100-fold less and shows exquisite selectivity across a large panel of histone lysine and arginine, and DNA methyltransferases. CPI-360 potently reduced global H3K27me3 and H3K27me2 levels in a dose dependent manner. CPI-360 effectively suppressed heavy H3K27me3 incorporation in KARPAS-422 cells without affecting total histone turnover.

References: Chem Biol. 2014 Nov 20; 21(11):1463-75.