PROTACs have shown unexpected advantages compared to the inhibitors of which they are composed. PROTACs can discriminate amongst highly homologous targets , and can exhibit much greater potencies than expected, due to a catalytic mechanism of action, which can compensate for low binary binding affinities or poor cellular permeability, and allow for use of weak, non-functional ligands . Unlike inhibitors, degraders must function beyond simple binary engagement. Instead they must work throughout a cascade of events, not only inducing proximity between two proteins which do not natively interact, but also yielding a productive ternary complex which structurally positions the target protein for efficient ubiquitination by the E3 ligase . Recent X-ray crystallographic structures and allied biophysical studies of PROTAC ternary complexes have demonstrated that some PROTAC-mediated ternary complexes are, like molecular glues, capable of cooperative binding, most notably shown for BRD4 BD2 -MZ1-VHL . This and subsequent studies have shown how in order to drive productive target ubiquitination and profound degradation at catalytic low concentrations, degraders need to form complexes of sufficient stability and residence time, which can be enhanced by cooperativity (defined as the ratio between the dissociation constant of a binary complex and that of the corresponding binding step in the ternary complex) and favourable intracomplex interactions . Such optimal "glueing" within the ternary complex can be challenging to realize with conventional PROTAC degraders that are by definition monovalent at the target of interest. Indeed, unfavourable PROTAC ternary complexes are often observed, which even if permissive to downstream protein ubiquitination and degradation, can lead to pronounced hook effect at higher concentration and/or result in slow and incomplete target degradation . We hypothesized that the molecular recognition process could be aided by multivalency and avidity, i.e. the accumulated strength of multiple affinities of individual binding interactions .