In vitro activity: Selectivity of CM-272 and CM-579 against 37 epigenetic enzyme targets including Bromodomain-containing enzymes (ATAD2A, ATAD2B, BAZ2B, BRD1, BRD2(BD1+BD2), BRD4(BD1+BD2), BRDT(BD1), CREBBP, TRIM24, TAF1), Histone methyltransferases (EZH1, EZH2, GLP, PRMT1, PRMT3, PRMT4, PRMT5, PRMT6, PRMT8, SETD2, SET7/9, SUV39H1, SUV39H2 and MLL-WARD), DNA methyltransferases (DNMT3A and DNMT3B) and histone demethylase (JMJD2A, JMJD2B, JMJD2C, JMJD2D, JMJD2E, JMJD3, JMJD1A, LSD1, Jarid1A, Jarid1B and Jarid1C) was performed by BPS Bioscience (.ph).

Kinase Assay: G9a and DNMT1 activities were measured using a time-resolved fluorescence energy transfer (TR-FRET). For G9a, TR-FRET is observed when biotinylated histone monomethyl-H3K9 peptide is incubated with cryptate-labelled anti-dimethyl-histone H3K9 antibody (CisBio Cat # 61KB2KAE) and streptavidin XL665 (CisBio Cat # 610SAXLA) after enzymatic reaction of G9a. For DNMT1, TR-FRET is observed when antibody specific to S-adenosylhomocysteine labelled with Lumi4-Tb (donor) is incubated with d2-labelled S-adenosylhomocysteine (acceptor), using the EPIgeneous methyltransferase assay (CisBio Cat # 62SAHPEB).

Cell Assay: Cell proliferation was analysed using the CellTiter 96 Aqueous One Solution Cell Proliferation Assay following the manufacturer's instructions (Promega, Madison, WI, USA). The GI50 values of the different compounds were determined using non-linear regression plots with the GraphPad Prism v5 software. Cell cycle assay is detailed in Supplementary Information. Apoptosis was analysed by flow cytometry using the FITC Annexin V Apoptosis Detection Kit I (BD Pharmingen) following the manufacturer's instructions. Details are provided in Supplementary Information.