Next, to assess and rank the ability of Homo-PROTACs to induce VHL dimerization, we developed and validated a novel rapid and convenient native gel electrophoresis assay (see SI, Figure ). The recombinant VCB protein complex (VHL:ElonginC:ElonginB) was incubated with the respective Homo-PROTAC for 30 min at room temperature and then separated via gel electrophoresis under nondenaturing conditions. Ternary complex formation was associated with an up-shift of the protein band in the gel, as observed for CM11. The 18-atom linker featuring Homo-PROTACs SH1, SH2, MeSH1 and MeSH2 led to the largest formation of the ternary complex, while other PROTACs only induced incomplete dimerization of VHL (MeCM11, alCM11, SH3, SH5) or formation of aggregates (SH5, MeSH3) (Figure ). Plotting the percent of ternary complex detected in the native gel electrophoresis assay against the pVHL30 degradation level observed in the initial PROTAC screen in HEK 293 cells at 1 µM for 8 h (see Figure ) reveals a clear correlation between the PROTACs' ability to induce ternary complex formation in vitro and inducing target degradation in cells (Figure ).