Figure 3.

(a) Relative levels of target protein are plotted against PROTAC concentration in media (i.e., concentration-degradation profile). For comparison, both the hook model presented here as well as the conventional $E_{\max }$ model are fitted to the data (see Figures S1 and S2 for further examples). When fitting the $E_{\max }$ model, only concentrations below the concentration of maximal degradation were considered. (b) A total of 17 concentration-degradation profiles were described using both the hook model and the $E_{\max }$ model. The resulting estimates for the maximal extent of degradation ($D_{\max }$) are plotted against the respective experimentally observed values. Experimental data (a,b) taken from Zorba et al. [21]. (c) The hook model is applied to reversible covalent (Cpd. α) and irreversible covalent PROTACs (Cpd. β). Data taken from Gabizon et al. [22]. (d) Protein levels after 6 h of incubation as well as levels after 24 h are plotted against the concentration of the non-covalent PROTAC Cpd. Y. The extended hook model (Equation (14)) is fitted to the concentration-degradation data from the 6 h time point, which then allows to predict degradation after 24 h. The experimental observations for the 24 h time point confirm that prediction. Data taken from Mares et al. [23].