21 - Hit-to-Lead and Lead Optimization (S2E6)

This episode describes the iterative process of refining "hits" into promising "leads" in drug discovery. We will explore how scientists balance potency, safety, and drug-like properties while making successive chemical modifications. The concept of structure-activity relationships (SAR) will be central to the discussion. We'll also integrate a case study, such as the development of SARS-CoV-2 antivirals, to illustrate the process of lead optimization and the challenges involved.

Further, we'll contrast predictive modeling with empirical optimization in lead optimization. We'll discuss the challenges of ensuring a drug can reach its intended target in the body and the complexities of drug resistance. The episode will also delve into the concept of reactive metabolites and how they can complicate drug development. We'll conclude with a discussion of the ethical considerations in drug development and the importance of balancing the benefits of new treatments with potential risks.