In order to explore whether other proteins could be subjected to degradation by bifunctional compounds incorporating arylidene-indolinones, we combined the BET protein ligand JQ1 8 with bromine-substituted indolinone 2. JQ1 has been used repeatedly for PROTAC development and a suitable site for linker attachment is established (Fig. ) . Ligands 2 and 8 were connected by a variety of different linkers (Supplementary Fig. ). All bifunctional probes induced degradation of BET proteins BRD2, 3 and 4 in Jurkat cells at 3 µM after 6 h treatment. Compounds 9 and 10 showed potent degradation activity, and were chosen for subsequent experiments (Fig. and Supplementary Fig. ). BRD2, 3 and 4 degradation by 9 is concentration-and time-dependent in Jurkat cells (Fig. ) and BRD2 depletion was also observed in Hep G2 and MDA-MB-231 cells (Supplementary Fig. ). Compound 9 induced degradation of BRD2 with a maximum level of degradation (Dmax) of 84 % at 3 µM and a half-maximal degradation concentration (DC50) of 255 nM (Fig. and Supplementary Fig. ). Up to 50 µM concentration, almost no hook effect was observed for BRD2 and BRD4, but at 10 µM, a strong hook effect was observed for BRD3 (Fig. ). BET mRNA levels were not reduced in Jurkat cells after treatment with 9 (Supplementary Fig. ). JQ1 (8) or 2 alone or in combination did not reduce BRD2 protein levels (Supplementary Fig. ).