Although the herein implemented ternary complextemplated DCC approach is currently applied to only one E3 ligase as target, we envisage it to be readily transferable to the development of Homo-PROTACs targeting other E3 ligases, especially those with available high-quality non-covalent small molecule ligands, such as for CRBN, MDM2, cIAP, DCAF1, TRIM58 or SOCS2. Beyond Homo-PROTACs, this disulfide-based ternary complex directed DCC approach could be further adopted to hetero-PROTACs, though requiring careful building block design (i.e., VHL binding building blocks featuring short linkers would be suitable for the development of hetero-PROTAC DCC approaches, as depletion of Homo-PROTACs with short linkers was observed in templated DCLs). Taking the concept of ternary complex-directed DCC assays one step further, other reversible chemistries used in conventional two-body DCC setting could be envisioned for this approach, e.g. oxime formation or boronate ester formation, which were recently established for reversibly assembled PROTACs by the Kodadek group. While generalizability beyond VHL as target remains to be shown, we believe that the ternary complex-directed DCC approach developed here offers the opportunity to fast-track hit identification in early-stage discovery programs for PROTACs and beyond for the identification of other bifunctional molecules as proximity-inducing modalities.