Medicinal chemistry

Many diseases can be traced to changes in how certain molecules, often proteins, function within cells. In many diseases, differences in cell signalling pathways exist between diseased cells and normal cells.

Targeted therapies are medicines that interact with a specific biological molecule, usually a protein. Targeted therapies can:

• Stop a molecule from working, called inhibition, or
• Encourage a molecule to work, called activation.

Many targeted therapies are ‘small molecules’, indicating the chemical’s size is much smaller than important biological molecules such as proteins or DNA.

There are many steps between finding a small molecule, or compound, that changes how a protein works, and it being available to treat people with a particular disease. Important features of potential medicines include:

• Stability, so the compound does not rapidly degrade before it can be used.
• Chemical properties including solubility and cell permeability, meaning the compound can travel through the body to diseased cells, and enter the cells.
• Specificity, meaning that the compound does not influence other molecules unrelated to the disease.

When small molecules are developed that have the potential to treat disease, they must undergo rigorous testing before they enter clinical use. The processes of pre-clinical testing and clinical trials are explained on our Clinical Translation page.

Knowing the three dimensional shape, or structure of a protein can give important clues about how it can be altered by a medicine. Our medicinal chemists work closely with structural biology researchers to develop new medications targeted to a specific part of a protein related to disease.

One of the most efficient methods of discovering new compounds that modify protein or cell behaviour is through the screening of large and diverse collections of small molecules. From this ‘chemical library’, small molecules that have the appropriate effect can be identified.

Chemical libraries can contain hundreds of thousands of distinct small molecules. These must each be tested in a consistent way to detect those compounds that have the desired effect.

In screening a chemical library it is important to include:

• A rapid screening method that allows screening of the entire library in a time-efficient way.
• A reliable readout that maximises the chance that a compound with the desired effect can be discovered, but minimises the chance of a ‘false positive’ compound that is wrongly detected despite not having the desired effect.

High throughput technology and powerful computing methods for analysing experimental data are important elements of screening.

Often, the small molecules discovered to have the desired effect may not have the best properties of a medicine. Medicinal chemists can make further chemical modifications to design a candidate new medication that is similar to the small molecule but has better stability, solubility and specificity.

Medicinal chemistry aims to develop new compounds that treat certain diseases, but the processes used can also advance other research into those diseases.

Chemical biology develops and uses small molecules to precisely inhibit a specific protein or biological process. This can be invaluable to research into that molecule or process, and lead to a better understanding of how certain diseases develop. Chemical biology approaches can complement other research fields such as genetics, cell biology and molecular biology, to understand a biological process.

In the long run, some small molecules produced by chemical biology research can be the basis of new medications.