In vitro activity: In KARPAS-422 cells, CPI-360 potently reduces global H3K27me3 and H3K27me2 levels with EC50 of 56 nM and 65 nM, respectively. CPI-360 also causes time-dependent transcriptional changes, and affects the viability of Y641N mutant EZH2-containing KARPAS-422 cells. In addition, CPI-360 gradually arrests KARPAS-422 cells in the G1 cell cycle stage followed by the induction of apoptosis.
Kinase Assay: CPI-360 is a potent, selectiveEZH2inhibitor with IC50 of 0.5 nM and 2.5 nM nM for wt EZH2 and Y641N EZH2, respectively.
Cell Assay: CPI-360 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 dosedependent manner. CPI-360 effectively suppressed heavy H3K27me3 incorporation in KARPAS-422 cells without affecting total histone turnover. CPI-360 treatment causes time-dependent transcriptional changes in germinal center B cell-like diffuse large B cell lymphoma. | 
