VHL and cancer: The anti-apoptotic BCL-2 family proteins(including BCL-xL, BCL-2, and MCL-1) are well-validated cancer targets,and dual inhibition is a promising therapeutic strategy.62,63 However, ABT-263, a potent dual BCL-2 and BCL-xL inhibitor, hasnot obtained regulatory approval due to its on-target thrombocytopenia.Thus, it was speculated that a PROTAC approach might avoid this sideeffect, since platelets express minimal levels of VHL, CRBN, and IAPs.To this end, DT2216 (4, Figure 6) was developed64 as the first PROTAC featuring a dual-targeting POI ligand.