PK/PD modeling of targeted protein degraders

This comprehensive review article in Drug Discovery Today, authored by Robin T.U. Haid and Andreas Reichel, explores the burgeoning field of targeted protein degraders (TPDs) and the critical role of pharmacokinetics/pharmacodynamics (PK/PD) modeling in their development. The authors have experience navigating the complexities of TPDs, contrasting their mechanism of action with traditional inhibitors and highlighting unique challenges such as the hook effect and event-driven pharmacology. The article analyzes various modeling approaches, categorizing them as empirical or mechanistic and retrospective or prospective, to guide researchers in selecting the most suitable tools for their specific questions in preclinical drug discovery. Furthermore, the authors share their experiences and insights from applying PK/PD modeling to internal degrader projects, addressing common challenges like data variability and irreproducibility, and offer an outlook on future opportunities for translational modeling in this rapidly advancing area of therapeutics. - NotebookLM