As a further example for arylidene-indolinone-based bifunctional degraders, compound 13 that is based on Ibrutinib 12 was explored (Fig. ). Ibrutinib inhibits BLK and BTK kinases with apparent IC50 values of 0.5 nM . Upon treatment of Ramos cells with degrader 13 for 6 h, BLK and BTK levels were reduced by 70% and 50%, respectively (Fig. ). Again, the proteasome inhibitor CFZ or neddylation inhibitor MLN4924 abolished degradation but treatment with the autophagy inhibitor CQ did not (Fig. ). These results demonstrate that bifunctional moieties composed of GW5074