In order to assess potential cytotoxic effects induced by the electrophilic indolinone moiety, BET ligand JQ1 (8), DCAF11 ligands 2 and 14, active bivalent degraders 9 and 10 and non-active compounds 15 and 16 were subjected to viability assays employing Jurkat and Hep G2 cells (Fig. and Supplementary Fig. ). Monovalent DCAF11 ligand 2, which embodies the electrophilic arylidene-indolinone scaffold, was only weakly antiproliferative in Jurkat-and Hep G2 cells (GI50 > 30 µM), whereas the covalent chloroacetamide DCAF11 ligand 14 showed higher toxicity in both cell lines, with GI50 values of 1.7 ± 0.2 μM and 6.5 ± 1.8 μM. Active JQ1-derived bivalent degraders 9 and 10 displayed antiproliferative activity in Jurkat cells with GI50 values of 0.09 ± 0.02 µM and 0.19 ± 0.03 µM. They are 6-to 10-fold more potent than nonelectrophilic compounds 15 and 16 which display GI50 values in the range of 1.0-1.2 µM. BET protein degradation was associated with induction of apoptosis . To analyze apoptosis induction by the DCAF11-targeting degraders, Jurkat cells were treated with JQ1 or compounds 9, 10, 15 and 16 for 18 h, followed by detection of caspase-3/7 activity. In the presence of degraders 9 and 10, caspase-3/7 activation was substantially higher than after treatment with JQ1 or non-active degraders 15 and 16 indicating that 9 and 10 are more potent apoptosis inducers than ligand JQ1 (Fig. ).