Supplementary Data – Table S1. Functional categories most significantly over-represented amongst genes, whose changed expression level following treatment with ES-285, correlates with increasing dose. A) Blood samples; B) Skin biopsies. Functional categories are ranked by the degree of their over-representation, based on a variant of the one-tailed Fisher exact probability (EASE score). Categories most highly over-represented are at the top. A) Blood samples EASE Functional Category score Gene Symbol cell proliferation 3x10-5 AIF1; ANAPC4; BAX; BCL2; BIRC5; CCNT1; CCNT2; CDC6; CDK2AP1; CDK4; CDK5; CDKN1B; CHAF1B; CHEK1; CHEK2; COL18A1; CSF1R; CUL4B; CXCL10; DLG3; DTYMK; ELK3; EMP2; EPS15; FGB; FLT1; FYN; GPS1; GSPT1; GTF2H1; HDAC3; HGF; HGS; HT014; HYPE; IFI16; IFRD2; IGF1R; ILF3; KATNA1; KLF4; KLK10; KRAS2; LIG3; LMNB2; MCM4; MET; MLH1; MSH2; MXI1; NBL1; NOL1; ORC1L; PDGFA; PNUTL1; PPARBP; PPBP; PPP3CB; PPP5C; PRKCA; PSIP1; PSMD8; PTEN; PURA; RAP1A; RBBP4; RBBP6; RBM11; RBM9; REV3L; RFC3; RFP2; RRM2; SCAND1; STAT1; STRN3; TFDP1; THPO; TM4SF9; TNFRSF5; TNFRSF7; TOB1; TOP1; TP53; UBE2V1; UBE2V2; VEGFB; VEGFC; WT1; ZNF259 cell cycle 1x10-4 AIF1; ANAPC4; BAX; BCL2; BIRC5; CCNT1; CCNT2; CDC6; CDK2AP1; CDK4; CDK5; CDKN1B; CHAF1B; CHEK1; CHEK2; CUL4B; DTYMK; ELK3; FYN; GPS1; GSPT1; GTF2H1; HDAC3; HGF; HYPE; IGF1R; ILF3; KATNA1; KLK10; KRAS2; LIG3; LMNB2; MCM4; MLH1; MSH2; NBL1; NOL1; ORC1L; PDGFA; PNUTL1; PPARBP; PPBP; PPP3CB; PPP5C; PRKCA; PSMD8; PTEN; PURA; RAP1A; RBBP4; RBBP6; RBM11; REV3L; RFC3; RFP2; RRM2; SCAND1; STAT1; STRN3; TFDP1; TOP1; TP53; UBE2V1; UBE2V2; VEGFB; VEGFC; WT1 G2/M transition of mitotic cell cycle 0.005 ANAPC4; BIRC5; CCNT1; CCNT2; CDC6; CDKN1B; CHEK1; GTF2H1; PTEN protein catabolism 0.01 ADAM15; ADAM9; ADAMTS10; AGTPBP1; ANAPC4; BLMH; BMP1; C1ORF35; C1R; C1S; CAPN2; CAPN3; CASP9; CDKL5; COPS7B; CPA3; CPB2; CTSB; DPP4; DPP7; FBXO11; FOLH1; HGF; IF; KLK10; LNPEP; LOC63929; M17S2; METAP2; MMP11; NDST1; NPEPPS; PSMD8; PSMF1; RNF13; SERPINE2; SIAH2; SMURF2; SUPT16H; UBE2B; UBE2I; UCHL3; USP1 S phase of mitotic cell cycle 0.01 CDC6; CDK2AP1; CHAF1B; LIG3; LMNB2; MCM4; MLH1; MSH2; ORC1L; PPARBP; PURA; RBBP4; REV3L; RFC3; RRM2; TOP1 G1/S transition of mitotic cell cycle 0.01 CCNT1; CCNT2; CDC6; CDK4; CDKN1B; CHEK1; GSPT1; GTF2H1; PTEN anti-apoptosis 0.02 BAX; BCL2; BIRC2; BIRC3; BIRC5; BIRC6; BNIP2; CCL2; IGF1R; PRDX2; TNFRSF6; TNFRSF7 negative regulation of cell cycle 0.02 BAX; CDK2AP1; KLK10; MLH1; MSH2; NBL1; PTEN; RAP1A; RFP2; TP53; WT1 mitotic cell cycle 0.02 ANAPC4; BIRC5; CCNT1; CCNT2; CDC6; CDK2AP1; CDK4; CDKN1B; CHAF1B; CHEK1; GSPT1; GTF2H1; HGF; KATNA1; LIG3; LMNB2; MCM4; MLH1; MSH2; ORC1L; PPARBP; PPP5C; PTEN; PURA; RBBP4; REV3L; RFC3; RRM2; TOP1 DNA replication 0.02 CDC6; CDK2AP1; CHAF1B; LIG3; MCM4; MLH1; MSH2; ORC1L; PPARBP; PURA; RBBP4; REV3L; RFC3; RRM2; TOP1 regulation of CDK activity 0.03 CCNT1; CCNT2; CDC6; CDKN1B; CHEK1; GTF2H1; PTEN ubiquitin cycle 0.03 BIRC6; FBXO11; HECTD1; ITCH; LOC92912; SMURF2; UBE2B; UBE2V1; UBE2V2; UBR1 humoral immune response 0.03 ADA; ADAR; BCL2; C1R; C1S; CCL2; CLECSF6; CSF1R; ENTPD1; IF; IRF4; ITGB2; TNFRSF5; TNFRSF7; YY1 B) Skin biopsies EASE Functional Category score Gene Symbol cell cycle 0.001 ABL1; ATR; AXIN1; BIRC5; CDC25C; CDK6; CETN1; CETN2; CHC1; CUL4A; CUL5; DCTN1; E2F3; E2F4; EREG; FGF7; FGF9; FNBP4; FOS; FZR1; HDAC7A; IFITM1; KIAA0241; LATS1; LIG3; LMNB2; MCM4; MCM5; MSH3; MSH5; MTCP1; NEK3; NF2; NOLC1; PARD6B; PARD6G; PB1; PGF; PPP6C; PRIM2A; PTN; RAD17; RAD50; S100A11; SH3BP4; SUGT1; TLK2; TSC1; TSC2; UBE1; UBE2V1; VAV1; VEGF mitotic cell cycle 0.003 ABL1; BIRC5; CDC25C; CDK6; CETN1; CETN2; CHC1; CUL4A; CUL5; DCTN1; FNBP4; FZR1; KIAA0241; LATS1; LIG3; LMNB2; MCM4; MCM5; MSH3; MSH5; NEK3; NOLC1; PB1; PPP6C; PRIM2A; RAD17; S100A11; SUGT1; UBE1 cell proliferation 0.009 ABL1; AREG; ATR; AXIN1; BIRC5; CD86; CDC25C; CDK6; CETN1; CETN2; CHC1; CSE1L; CSRP2; CTBP2; CUL4A; CUL5; DCTN1; E2F3; E2F4; EMP3; EREG; FGB; FGF7; FGF9; FNBP4; FOS; FZR1; GAB1; HDAC7A; HDGFRP3; IFITM1; KIAA0241; LATS1; LIG3; LMNB2; MCM4; MCM5; MSH3; MSH5; MTCP1; NEK3; NF2; NOLC1; PARD6B; PARD6G; PB1; PGF; PPP1CB; PPP6C; PRIM2A; PRKAR1A; PTN; RAD17; RAD50; S100A11; SH3BP4; SUGT1; TLK2; TM4SF9; TPD52L2; TSC1; TSC2; UBE1; UBE2V1; VAV1; VEGF nuclear division 0.02 CDC25C; CETN1; CETN2; CHC1; DCTN1; FZR1; LATS1; LIG3; MSH5; NEK3; NOLC1; PB1; RAD17; RAD50; SUGT1 biological_process unknown 0.03 ABCC4; ABL1; ADFP; BCL7B; C14ORF118; C16ORF34; CALR; CAMK2G; CH-TOG; CLSPN; COL5A3; CSRP2; CXADR; CYYR1; DCPS; DJ167A19.1; DLK1; DMD; DOM3Z; DSCR5; EIF2A; EIF3S2; ELF2; FAM3C; GPR107; IFIT1; LMNB2; LOC340186; LRPPRC; LRRFIP2; PIGM; PLAC1; PPIL2; PRCC; RBMX; SDC2; SH3BP4; TGM2; WDR9; WWOX; ZNF198 M phase 0.03 CDC25C; CETN1; CETN2; CHC1; DCTN1; FZR1; LATS1; LIG3; MSH5; NEK3; NOLC1; PB1; RAD17; RAD50; SUGT1 telomere maintenance 0.04 HNRPD; RAD50; TINF2; TNKS2 coenzyme and prosthetic group 0.04 ATP6V1F; COQ6; COX10; GCLM; GSR; HMOX1; HPGD; MTR; PANK3; PDHA1; RDH5; WWOX metabolism S phase of mitotic cell cycle 0.04 ABL1; FNBP4; KIAA0241; LIG3; LMNB2; MCM4; MCM5; MSH3; MSH5; PRIM2A; RAD17; S100A11; UBE1 mitosis 0.05 CDC25C; CETN1; CETN2; CHC1; DCTN1; FZR1; LATS1; NEK3; NOLC1; PB1; RAD17; SUGT1 amino acid biosynthesis 0.05 ALDH4A1; ASNS; CTBP2; HPGD; MTR; RDH5; WWOX M phase of mitotic cell cycle 0.05 CDC25C; CETN1; CETN2; CHC1; DCTN1; FZR1; LATS1; NEK3; NOLC1; PB1; RAD17; SUGT1 .