Substantive evidence supports the notion that optimizing for ternary complex affinity and stability provides a robustly validated and, in most cases, successful criterium for optimizing degradation activities of PROTACs. For example, correlations have often been observed between a PROTAC's ability to form stable ternary complexes at low concentrations and its degradation efficiency and potency. From this rationale, we therefore posited that DCC could be applied in a new fashion to screen for and identify most promising PROTACs in experiments where stabilization of reversibly assembled PROTAC library members is governed by E3:DCC-PROTAC:POI ternary complex formation. In this context, both E3 ligase and POI would act jointly as templating moiety to thermodynamically stabilize and consequently enrich DCC-PROTACs able to form a stable ternary complex (Figure ), while discriminating against species that are less able to induce ternary complex formation. We therefore embarked on a study to develop and apply a proof-of-concept for a DCC-PROTAC approach.