CHAPTER 1. Modulation of Biological Targets Using Allosteric Ligands: Food for Thought

Research in life sciences is witnessing the emergence of new knowledge at a greater pace than ever before. This is starting to translate into innovative therapeutic treatments and approaches. The use of chemicals to modify the course of human disease has evolved into a number of modalities, which may arbitrarily be classified as biologics or small-molecule treatments. Some of the characteristics of these two are compared and contrasted. The term “allosteric modulators” is generally used to describe small molecules that change the attributes of large biological macromolecules, such as membrane-bound receptors, ion channels and transporters, as well as soluble enzymes. The rationale that stimulated the research into allosteric drugs in the mid-1990’s is presented, including perspectives on the early learnings that have emerged such as “flat structure–activity relationships” and “functional switches”, and how subtle differences in mechanisms of allosteric modulation can impact drug discovery.