MS147 selectively degrades BMI1 and RING1B over PRC2 core components and is selective for EED over 20 methyltransferases and 12 epigenetic reader domains. a) The effect of MS147, PROTAC 2, and EED226 on reducing the protein levels of EED, BMI1, RING1B, H2AK119ub, EZH2, SUZ12, and H3K27me3. K562 cells were treated with DMSO or the indicated compound at the indicated concentrations for 24 h. b,c) The effect of MS147 on reducing the EZH2, SUZ12, and H3K27me3 protein levels in K562 cells treated with MS147 at a range of concentrations for 24 h (b) or 5 µ
m of MS147 for indicated times (c). The protein levels of EED, BMI1, RING1B, H2AK119ub, EZH2, SUZ12, and/or H3K27me3 in panels a–c were determined by WB with vinculin and/or H3 as the loading controls. The WB results shown in panels a–c are representative of two independent experiments. d,e) The effect of MS147 on inhibiting 20 methyltransferases in biochemical assays (d) and binding 12 epigenetic reader domains in in vitro thermal shift assays (e). MS147 was tested in these selectivity assays at 10 µ
m. Data shown are the means ± SD from duplicate experiments.