My medicine: Drug discovery

 

Drug companies are continually searching for new compounds to develop into acceptably safe and effective medicines that can:

• Relieve troublesome symptoms
• Prevent disease from taking hold
• Slow down the course of a disease
• Potentially cure disabling and/or lethal conditions

Finding suitable compounds, which stand the best chance of becoming effective medicines, is a process of elimination. This discovery phase takes several years and requires a wide range of skills and expertise.

Ideas for drug development
Many different factors influence the development of new medicines. These include:

• Advances in the understanding of human biology and healthcare, such as stem cell research and gene therapy, which help scientists piece together how a disease is caused and what processes in the body are involved
• Government treatment priorities—diabetes and heart disease, for example
• An ageing population, among whom diseases, such as Alzheimer’s disease and cancer, are more common
• Global initiatives, such as those to halt new cases of malaria and HIV infection, for example
• The availability of research funding and sponsorship
• The costs and effectiveness of existing medicines
• Chance findings, which shift the focus of research. For example, Viagra was originally developed to relieve the chest pain of heart disease. But during tests, men said it helped them with erectile problems, and it was subsequently developed for this purpose instead.

The search for a new compound
Scientists start by either targeting a known step in the disease process or working out how a disease is caused. They then pinpoint a stage that can potentially be altered or interrupted.

This might be interfering with the production of a particular chemical, or the way in which certain cells interact, or a process that switches a gene on or off, for example.

Once the “target” has been identified, the hunt begins to find suitable compounds. These can be sourced from:

• An existing reserve of chemical compounds built up over many years
• Design changes to the make-up of an existing medicine
• Combining compounds to make a new one

Special tests to screen for the unique properties of the compounds also need to be developed.

Weeding out unsuitable compounds
Millions of compounds will be tested to see if they have any impact on the intended target(s). Many won’t. But of every 1000 that do, called hits, just 30 will be suitable for testing further at varying strengths, on different cells and under different conditions to see if they still have an effect. Those that do are called lead compounds.

Scientists will want to know if a new entity is likely to:

• Be stable under different conditions
• Behave consistently
• Be harmful
• Pass into cells efficiently
• Reach its chosen target effectively
• Be selective rather than indiscriminately knocking out several other related targets

Commercial factors also come into play. The drug company will want to know if the compound is unique so that its originality can be protected (patented) and if it is going to be suitable for manufacture on a large scale.

Usually only a dozen entities will meet all these criteria, to be developed further―a process known as lead optimisation—with the aim of being subsequently tested in pre-clinical research.