Similar to the observations made for PDE degradation, treatment with the autophagy inhibitor CQ did not prevent degradation, whereas in the presence of the proteasome inhibitor CFZ or the neddylation inhibitor MLN4924, no degradation was observed (Fig. ). These findings suggest that also degradation of BRD2 proceeds via the UPS and not by autophagy. Compounds 9 and 10 carry a bromine-substituent in the 5-position of the indolinone, whereas in GW5074 an iodine occupies this position. To determine whether the kind of halogen influences BET-protein degradation, Jurkat cells were treated with compound 10 and its iodo analog 11. Both compounds 10 and 11 degrade the BRD2 protein with comparable efficiency and BRD2 depletion was abolished by pre-treatment with proteasome-or neddylation inhibitors but not by autophagy inhibitors (Supplementary Fig. ). Wang and Ouyang et al. recently reported that close analogs of 11 induce degradation of BRD4 through autophagy (Supplementary Fig. ) . Attempts to confirm this finding for a selected compound again indicated degradation of BRD4 and BRD2 by means of the proteasome (Supplementary Fig. ).