VHL and leukemia: Due to low expression levels of VHL in platelets, on-target toxicity of DT2216 was considerably reduced compared to its parent inhibitor, thus rescuing its therapeutic potential, and recently enabled advancement of DT2216 as first VHL-recruiting PROTAC into phase I clinical trials.144,145 Exploiting a different exit vector for linker attachment on ABT-263 furthermore enabled the development of Bcl-xL and Bcl-2 dual degraders showing improved antitumour activity in leukaemia cells which are depending both on Bcl-xL and Bcl2 for survival.146