Mathematical models predict a bell-shaped dependency on PROTAC concentration. At high concentrations, ineffective binary complexes are observed, which compete with effective ternary complexes. Competition leads to a decline in the formation of ternary complexes, ultimately impacting the potency of the PROTACs. This is known as the ‘hook effect’. Mass photometry can be used to quantify relative concentrations of intermediate species and assess their cooperativity effects. More specifically, you can determine the concentration range where maximal complex formation occurs and identify PROTAC compounds with significant positive cooperativity in the ternary complex, which do not present an observable ‘hook effect’.