This episode focuses on early assessments of absorption, distribution, metabolism, and excretion (ADME) in drug development. We will discuss how these assessments ensure that drug candidates are "drug-like" and explore Lipinski's Rule of 5 as a key guiding principle. Real-world examples of ADME screening in practice will be provided, along with exceptions to Lipinski's rule, particularly for biologics and PROTACs. Early ADME/Tox models and high-throughput permeability testing will also be discussed.

The episode will also delve into the importance of understanding drug metabolism, including the formation of metabolites, both helpful and harmful. We'll explore the darker side of metabolism, discussing reactive metabolites and the challenges they pose for drug development. The episode will conclude with a look at the future of ADME research, highlighting the exciting role of the microbiome and the potential for personalized medicine.