UNC 2400, a close analogue of UNC1999, is a negative control of UNC1999 that inhibits EZH2 and EZH1 . Histone-lysine N-methyltransferase (EZH1 or EZH2) is the catalytic subunit of the polycomb repressive complex 2 that catalyzes methylation of histone H3 lysine 27 (H3K27). The trimethylation of H3K27 (H3K27me3) is a transcriptionally repressive post-translational modification. Hypertrimethylation of H3K27 and overexpression of EZH2 are involved in cancers . UNC 2400 is a negative control of UNC1999. UNC 2400 inhibited EZH2 with IC50 value of 13 µM and exhibited >1,000-fold less potency than UNC1999. Also, UNC 2400 inhibited EZH1 and EZH2 Y641F with IC50 values of 62 and >200 µM, respectively. In MCF10A cells, UNC 2400 exhibited little inhibition of H3K27me3 levels and had low cellular toxicity with EC50 value of 27.5 µM that was similar to UNC1999. In DB cells, UNC 2400 (3 µM) did not significantly inhibit DB cell proliferation and had no influence on H3K27me3 or EZH2 levels .