Figure 5.

(a) The $PD$ model is fitted to data on the downstream pharmacodynamic response (TNF-alpha levels) in the presence of various concentrations of the lead compound (Cpd. X). This analysis yields the target protein levels of half-maximal pharmacodynamic response ($P_{50}=87\%$) and an empirical hill coefficient ($n=7$). Subsequently, a target profile is defined for a potential follow-up compound (Cpd. Y). (b) Target protein levels (RIPK2) are plotted against drug concentration. The $PD$ model is used to predict the target concentration-degradation profile for the follow-up compound from before (Cpd. Y). (c) The downstream pharmacodynamic response (TNF-alpha levels) is plotted against the concentration of the corresponding non-degrading (nd) control compounds. (d) The observed TNF-alpha response is plotted against the corresponding RIPK2 levels for both compounds. The dashed line shows the fitted $PD$ model from before, but this time explicitly neglecting inhibition ($I=0$). Experimental data (a–d) taken from Mares et al. [23].