A Pharmacology Primer Techniques for More Effective and Strategic Drug Discovery

1. Dr. Kenakin, your extensive background in both academic and industrial pharmacology research uniquely positions you to write a book like "A Pharmacology Primer." Can you share what inspired you to write this book and how your experiences influenced its content?

Actually, the beginnings of this book were instigated by a need to educate newly hired biology and chemistry staff who had no background in pharmacology when they joined the company where I worked, GlaxoSmithKline. We realized there was no source of information and I wrote the course which then became a book.

Other books simply discussed the use of drugs for treatment of various ailments but not how to make and improve them.

2. In your book, you emphasize the application of pharmacology in drug discovery. What are some of the most significant changes you've observed in this field over the years, and how does the 6th edition address these changes?

Pharmacologists are almost always working in systems they do not fully understand… physiology and Nature still hold many mysteries. This being the case, pharmacology is uniquely based on new technologies to unveil these new secrets of physiological system and thus, it is a fast paced field of endeavor requiring regularly updated information.

Genomics, bio and chemoinformatics, structural biology, highthroughput technologies, and virtual screening have transformed pharmacology in the past few years and technologies such as AI promise to do more of this.

3. One of the key themes in your book is the breakdown of complex discovery techniques. Could you elaborate on how binding, functional, orthosteric, and allosteric assays contribute to quantifying drug effects and their therapeutic applications?

These are the building blocks of Pharmacologic research that form the framework of discovery. Two fundamentally different approaches to the study of drug-target interaction are through binding (physical measurement of molecules binding to protein) and function (measuring the cellular consequences of drugs binding to targets). Each of these have their strengths and limitations and yield complimentary information.

Two other fundamentally different approaches measure the actual interactions of molecules and targets: orthosteric and allosteric. Orthosteric basically measures the ‘steric hindrance' of bodies interfering with each other as they compete for a common binding site. Allosteric is where drugs bind to a separate site on the target to modify physiology through changing the shape of the protein.

4. The book discusses the use of new technologies for screening, such as virtual, DNA-encoded libraries, and fragment-based approaches. How have these technologies revolutionized the process of drug discovery, and what future advancements do you foresee in this area?

Basically all of these technologies have drastically increased the scope and capacity to test vast numbers of chemical structures. Before the advent of these technologies, libraries of thousands of compounds could be tested with robotic screening; with these new approaches, millions to billions of new structures can now be tested and this radically enhances the chances of finding fruitful binding ‘hits'.

It is defensible to say that probably now any target in physiology can be ‘drugged' (i.e. a molecule found that binds to it).

Discover more: https://www.pharmafocusamerica.com/research-development/a-pharmacology-primer