Subasumstat induces cell death in MM cell lines. (A) Treatment of five MM cell lines with 250 nM subasumstat inhibits 2/3 SUMOylation and increases the pool of free SUMO2/3 compared with dimethyl sulfoxide (DMSO)-treated control cells. (B) Expression of indicated core SUMOylation machinery genes in a panel of MM cell lines (data derived from depmap.org). TP53 status is indicated for each cell line. (C) Subasumstat monotreatment on a panel of five MM cell lines. Cells were treated for 3 days with different concentrations of subasumstat; subsequently, viability was measured. Results of 3 independent measurements are shown. (D) Top: OPM2 cells were treated for 16 hours with DMSO or subasumstat and analyzed by quantitative proteomics. Bottom: fgsea plots of quantitative proteomics data. DNA repair and apoptosis proteins are significantly upregulated in subasumstat-treated OPM2 cells over DMSO-treated control cells. P-adj, adjusted P value; Suba, subasumstat.