Our proteomics analysis (Fig. ) showed SIM1 induced decrease in protein levels of HMOX1 (heme oxygenase 1) suggesting early initiation of apoptosis . Early and late apoptotic induction between compound treatment was compared and notably, SIM1 induced a much greater degree of both early and late apoptosis at 1nM compared to all bivalent counterparts tested, even when compared to tenfold higher concentration of (R,S)-SIM1, MZ1, or MT1 (Fig. and Extended Data Fig. ). Together, the biological data supports more potent degradation and more substantial downstream functional activity of the trivalent degrader SIM1 compared to parent bivalent degraders or inhibitors.