Heterobifunctional protein degraders like PROTACs are one of the most important types of targeted protein degraders. However, beyond the rule of 5 nature of these compounds introduces distinct ADME challenges not commonly encountered with smaller molecules. These challenges include poor solubility, low permeability, inadequate recoveries in in vitro ADME assays, high protein binding, and weak in vitro-to-in vivo correlation (IVIVC). This webinar focuses on ADME strategy and challenges in developing heterobifunctional degraders and the possible solutions to overcome hurdles.