Outline of Contents

  1. Principles and Terminology
    The drug discovery pipeline
    Selecting drug targets
  2. Essential Protein Chemistry
    Detailed analysis of polypeptide structure
    Bonding interactions in polypeptides and proteins
  3. The ACE Inhibitors
    Targeting enzymes
    The development of Captopril
    Mode of action of the ACE inhibitors
    Advances after Captopril
  4. Lessons from Captopril
    Molecular drug design
    Role of the common functional groups
    Optimisation strategies
  5. The Statins
    Targeting cholesterol
    Mode of action of HMG Co-A reductase inhibitors
    The development of Atorvastatin (Lipitor)
  6. The Role of Receptors
    Receptor mechanisms
    The development of Cimetidine and Zantac
    Kinase-linked receptors The development of Imatinib (Gleevec)

Recommended Texts and Support

Background and Acknowledgements

The strategies and logistics of drug discovery have evolved over many decades, underpinning major advances in healthcare, as well as the growth of global industries. These pages offer an introduction to the practices of drug development, illustrating the principles of target identification, drug design and screening, target validation, lead identification and lead optimisation. Key stages in the sequence are illustrated with case studies from the last 60 years, which saw the exploitation of natural product chemistry and the emergence of modern drug design strategies. These web pages are designed to support UG chemistry courses, the intention being to illustrate the principles of drug development at the molecular level. Interactive molecular models are included so that structures can be explored in depth. The files utilised in the case studies are freely available from the Protein Data Bank (PDB). They can be viewed online at the source, or downloaded for visualisation as interactive 3-D models using modelling software, in this case the JSmol molecular viewer.

The original version of this site supported a UG chemistry unit entitled Fundamentals of Drug Discovery, provided for Level 2 MChem students in the School of Chemistry of the University of Manchester. The prescribed course text was An Introduction to Medicinal Chemistry by Graham Patrick, and I must acknowledge my extensive use of this excellent book in illustrating some aspects of the syllabus — I strongly recommend it to anyone seeking a broader and deeper coverage of medicinal chemistry at the molecular level. The web files were revised to improve their device compatibility and visual quality, and I thank Stuart Anderson for providing the template which made this task straightforward. This revision was completed during the COVID-19 lockdown of 2020, and the website is henceforth dedicated to the workers of the UK National Health Service (NHS). To donate to this cause, visit NHS Charities.

Tim Wallace
Manchester, May 2020