Many questions have to be answered before a pharmaceutical research project can be launched. For which diseases is there an urgent need for new medicines? Are there any new findings about the causes of a disease? Can the side effects of existing medicines be reduced?
If the answers to most of these questions are positive, the long and risk-fraught process of developing a new medicinal product begins. It starts with the identification of a target. This is a point of attack within the body that either triggers or has a fundamental effect on the disease process. The new medicine needs to act on this point of attack in such a way that the disease subsides or is relieved. These targets are usually enzymes or receptors.
Lock and key principle
Once a suitable target has been identified, the next step is to identify a suitable active substance. Large-scale testing using automated processes (known as high-throughput screening) exposes the target to up to 200,000 different compounds every day and tests these combinations for interactions. An interaction occurs when a substance either inhibits or activates the target.
A good analogy here is a lock and key. The target being studied represents the lock. Only a few of the many active substances – or “keys” – being tested against the target will actually be a good fit.
Substances that react with the target are called hits and subsequently undergo further testing to establish their potency. On average, out of 5,000 to 10,000 hits tested, only 20 are suitable for further investigation.
From hit to active substance
Since the hits, i.e. the compounds that have reacted with the target, are not suitable for use as active substances in their original form, they are chemically modified to give them the properties they need as a new pharmaceutically active substance. Continuing the lock and key analogy, we could say that the key fitted into the lock before but was very difficult to turn, so the desired effect was either too weak or didn’t happen at all. The key now needs to be modified so that the lock can be opened easily.
An active substance needs to fulfil a number of requirements before it can act as the right key for the lock. For example, if possible it should not affect any processes in the body other than the target for which it is being developed. This development can take several years while researchers add or remove individual parts of the active substance in order to further optimise its properties. Each modification is subsequently tested. If the substance is satisfactory after a few years and several hundred changes, the pharmaceutical company applies for it to be patented. This ensures that no company other than the pharmaceutical company that developed this new active substance can use it to manufacture medicines. The patent application marks the start of the 20-year period of patent protection, well before it is clear whether the active substance will ever reach the market as a medicinal product.