Protein-protein interactions (PPIs) play a substantial role in essential biological processes . Modulating protein functions or inducing targeted protein degradation using PPI stabilizers has become a promising therapeutic strategy, which covers a broad range of physiological processes such as degradation, inhibition, stimulation, and translocation . In particular, proteolysis-targeting chimeras (PROTACs) consisting of a linker between an E3 ligase-binding and a target-binding warhead to facilitate ubiquitination and subsequent degradation of the targeted protein . According to the mathematical models for noninteracting proteins, the equilibrium concentration of the ternary complex can be analytically determined given the initial concentration of each species (i.e., the two protein partners and the ligand), the dissociation constants of the two protein-ligand pairs, and the intrinsic cooperativity (of the ligand, denoted as α) . In a non-cooperative system, the ternary complex forming species must possess some binding affinity to both proteins to induce the formation of a ternary complex, termed the dual-binding mechanism . However, unmeasurable low binding affinities have been observed in many ternary complexes induced by molecular glues . Systems that do not follow the dual-binding mechanism can still form ternary complexes through high cooperativity, including allosteric modulation . Structural determinations and mutagenesis studies have shown that cooperativity is directly related to the induced de novo protein-protein contacts and is orthogonal to the binary protein-ligand binding affinities . PROTACs can hence induce favorable or unfavorable PPIs to exhibit positive (α > 1) and negative (0 < α < 1) cooperativity through different scaffolds of the linker, respectively. Furthermore, high cooperativity mitigates the notorious hook effect seen for bifunctional PPI stabilizers, which starts to become already disruptive around compound concentrations that are one log unit below the corresponding ternary K d values . The dual-binding mechanism requirement and the partner-specific induced PPIs make PPI stabilizers highly selective and attractive therapeutic alternatives .