While the chemical design and synthesis of a trivalent PROTAC is more involved than for bivalent ones, the increased effort showed significant benefits and allowed to overcome these perceived challenges, affording a much-improved degrader. To achieve this, outlined is a new linker design strategy for generation of a branched trifunctional scaffold to which both target and E3 binders could be conjugated, which provides highly modular design and opens to numerous future applications (Fig. ). Though we have shown here increased valency to address two repeat domains within a target, trivalent compounds could be directed towards two distinct domains on the same protein. A multivalent design concept could be applied to any three protein targets if binding ligands for each are known, wherein all three warheads engage if structural constraints allow (Fig. ). Multivalent avidity may allow leveraging weak intramolecular binding at the ternary complex interface, and best exploiting weak binding ligands which can be readily found but can be challenging to optimize as part of mono-or bivalent agents . One might imagine two subunits within a multi-protein complex, or even two distinct proteins (albeit at the expense of avidity), could be recruited either simultaneously or independently to the E3 ligase. While this manuscript was in advanced stages of revision, a dual-target PROTAC compound consisting of three warheads was reported, however not shown to engage all three warheads simultaneously as we report here.