To test the hypothesis of ternary complex-directed DCC PROTAC screening, our system had to fulfill the general requirements of DCL experiments: namely, reversible chemistry with reaction conditions that are tolerated by the proteins introduced as templates; the reaction rates should be sufficiently fast in the interest of protein stability and experimental efficiency; and the equilibrium state has to be frozen prior to library analysis without chemical modification of the reversibly assembled DCC-PROTACs. Beyond that, the reversible bond introduced into these PROTACs needs to be sufficiently stable to allow independent synthesis and isolation of the unmodified DCC-PROTACs for biophysical and biological testing. This last point is vital in this work to unambiguously correlate amplification observed in the DCC experiments with the biophysical and cellular activity of the PROTAC, thus allowing to validate the concept of ternary complex formation as a driving force for amplification in the DCC assay.