Drug Information Q&A Q53: What kinds of efforts are being made to find the source of drugs?

Answer

In the past, we searched for drug elements from natural ingredients, but recently we have been searching for drug elements from chemical compounds. We have robots instead of people testing the efficacy of hundreds of thousands of compounds, or synthesizing compounds after predicting their efficacy with a computer in advance.

Explanation

Drugs begin with the discovery of the substance that will become the drug substance. There are various ways to do this.

The first is to extract the drug substance from natural materials such as plants, animals, and microorganisms. In ancient times, aspirin was created from the active ingredient of willow. Penicillin, the world's first antibacterial drug, was also derived from an ingredient produced by blue-green algae. There are several drugs that many people use today that are derived from natural ingredients, and it is likely that more and more drug elements will be discovered from natural ingredients in the future.

The second method, which is currently the mainstream method, combines a "compound library," which collects a vast number of compounds, with a computer-based development system called "high-throughput screening" to search for drug elements.

Pharmaceutical companies have a vast library of original compounds based on their accumulated research to date. From these, the compounds are sorted and screened for efficacy and other characteristics (this is called "screening").

In the past, the only way to do this was to manually measure the efficacy of each individual compound, but today, computer-controlled robots are used to screen automatically and at high speed. This system is high-throughput screening.

The third method is to screen a huge number of compounds all at once on a computer. First, millions of compounds are created on a computer and screened by simulation. Only those substances that have been selected and sifted in this way are actually chemically synthesized and screened. This method greatly increases the probability of finding promising drug substances.

Once a drug element is found, the structure of the substance is chemically altered to improve its efficacy and safety and to create a better drug.

In most cases, drugs target proteins in the body in order to exert their effects. If the target protein is compared to a keyhole, the substance that forms the key is first found, and then the key is modified to fit perfectly into the keyhole. In recent years, the three-dimensional structure of the target protein has been elucidated in an increasing number of cases, and drugs can now be improved efficiently.

SPring-8, a large synchrotron radiation facility, is a representative example of such a facility. Synchrotron radiation, which is 100 million times brighter than the sun, makes it possible to elucidate the structures of proteins and other substances that are the basis of diseases. The X-ray free electron laser SACLA is also being used.

Furthermore, research has begun to analyze the structure of proteins, which are the basis of diseases, at various levels of size, and to consider treatment methods based on a comprehensive judgment of the protein structure. This method is called "omics analysis," and research has begun at major medical facilities across Japan using five types of omics analysis to develop new drugs for 11 diseases, including cardiovascular diseases and cancer, for which countermeasures have been pointed out as important in recent years.