Introduction

Drug discovery, from concept to clinic, is a complex and expensive process involving the work of an escalating number of people and resources over many years. A major component of this cost has been the attrition rate of medicines that reach the development stage but then fail as the result of adverse toxicity or only limited effectiveness against the target disease. In recent years much greater attention has been paid to addressing the problems of attrition at an earlier stage in the discovery process and moving the focus of research away from a strategy based purely on potency against the isolated target protein. It begins with practical, multidisciplinary, laboratory work leading to the identification of candidate molecules that are evaluated in large multinational clinical trials. The escalating costs are mirrored by the increasing demand for the supply of the compound as development work proceeds. Typically, a hit is identified from a few milligrams of the compound; preliminary pharmacokinetics and efficacy determination will typically require hundreds of milligrams to grams of material, escalating to perhaps kilograms for preclinical safety and pharmacy evaluation. By the time human trials are initiated, tens to hundreds of kilograms are often necessary; production may entail quantities measured in tonnes.

Course learning outcomes

After studying this course, you should be able to:

• Appreciate the intrinsic difficulties associated with developing a drug molecule from conception into a medicine suitable for clinical use
• Appreciate how molecular modeling can be used in the drug discovery process
• Understand the historical background to pain control
• Understand that opioids, steroids, and NSAIDs all work at the molecular level
• Appreciate that anti-inflammation drug discovery requires a detailed understanding of the biochemical processes that constitute the inflammatory response.