E3 ligases are a class of enzymes that are involved in ubiquitin-mediated protein degradation, and they play a critical role in many cellular processes, including cell cycle regulation, DNA repair, and apoptosis. Selective targeting of E3 ligases has emerged as a promising strategy for developing novel therapeutics for various diseases, including cancer . Thus, predicting the target binding selectivity for E3 ligases using pharmacophore analysis can be useful in designing focused libraries for screening campaigns. With the help of this, we can not only enrich existing libraries with high probability candidates, but in the long run, also define geometric and interaction rules for each E3 ligase. Overall, this binding selectivity will facilitate rational design of future proteolysis targeting chimera (PROTAC) and novel molecular glues.