Chemical Biology: Approaches to Drug Discovery and Development to Targeting Disease

Chapter 11: The Role of Chemical Biology in Understanding and Treating Disease—Are Small Molecule “Correctors” the Way of the Future?

David Selwood

Wolfson Institute for Biomedical Research, University College London, London

In this section, we take on a diverse group of diseases, including those related to mental health, metabolism, and protein trafficking and misfolding, and show how chemical biology has impacted the study of these diseases. An intriguing theme emerges from these reviews: the influence of genetics on the understanding of disease. It has been 12 years since the publication of the human genome, and the early hype surrounding its publication was not translated into instant gains in the understanding of diseases and the search for new molecularly targeted medicines. Now we have genomewide association studies (GWAS), pointing to either outright genetic causes for disease or associations that, when combined with environmental factors, can lead to disease. Perhaps it is the combination of this knowledge with the advent of a new type of therapeutic agent, small-molecule “correctors” of protein function, which will yield the biggest gains. Small molecules such as the Vertex cystic fibrosis drug offer a precisely tailored genetic medicine for the treatment of cystic fibrosis, correcting aberrant protein function at the level of the gene product.

In simpler organisms, the effect of genetic changes is already evident and plays a major role in the design and development of ...