Figure 7.

Our modeling framework can be used to address three major questions, each associated with one of the pillars of translational pharmacology (see Figure 1 and Figure 2 for color coding). The hook model is fitted to the concentration-degradation profile yielding three parameters which can be used to assess PROTACs as degraders. The $k_{\mathrm{cat}}$ model allows to predict what binding affinities are necessary to achieve the desired degradation, thereby giving rational guidance to lead optimization efforts. The $PD$ model translates protein degradation to a defined biomarker response. This is particularly useful when it comes to identifying a target value for protein degradation.