The success of proximity-inducing modalities, such as PROTACs, crucially depends on the formation of a stable ternary complex. Herein, we establish that this ternary complex can be exploited as selection criterium in multi-protein templated DCLs by driving enrichment of proximity-inducing library members. Using a disulfide-containing VHL-targeting Homo-PROTAC system as proof-of-concept, we demonstrate that the developed ternary complex-directed DCC assay enables quick identification of novel VHL degraders from library mixtures. Comparison of the performance of DCL members in a templated library with their biophysical and cellular potency shows overall good correlation between their ability to induce VHL dimerization and cellular degradation activity and their enrichment in the DCC assay. Conversely, non-degrading PROTACs and monomeric species were depleted in the templated DCL, indicating that amplification is indeed driven by cooperative ternary complex formation, and not a result of binary protein-library member binding events. Besides confirming previously tested degrading disulfidecontaining Homo-PROTACs as hits, i.e., SH2 and MeSH2, further novel hits were identified using this strategy. For instance, H2-H4 identified in the very first ternary complex-directed DCC experiment, was validated as excellent mediator of ternary complex formation outperforming SH2, and as potent VHL degrader, leading to rapid depletion of pVHL30 levels in cells.