Similarly, a site for E3 ligase ligand attachment came from the co-crystal structure of the bivalent BET inhibitor MT1 (2) bound to two monomers of BRD4 (Fig. ). In contrast, the bivalent inhibitor Bi-BET is fully buried in its co-crystal structure (Extended Data Fig. ), therefore we elected MZ1 (1) and MT1 (2) as the progenitor bifunctional molecules in our design strategy.