By selecting the most appropriate target structures, using new technology platforms such as ultra high-throughput screening and genetics, we will be able to discover and develop drugs that offer unprecedented efficacy and safety.


New Technologies
New technologies and areas of research are the basis for today's revolution in medicine. Some of these have emerged over the past few decades, others more recently. Molecular biology and its most important instrument, genetic engineering, make it possible to study biological processes in cells, organs and organisms at the level of biomolecules. The causes of diseases can be identified. Thus it was discovered, for example, how the human immunodeficiency virus (HIV), the virus that causes AIDS, penetrates and destroys white blood cells. In combination with information technology, automation and new chemical techniques, biosciences have the tools to develop new and better drugs.


Genomics and Bioinformatics
With the help of genomics and bioinformatics, researchers can identify genes and mutations in genes which, though currently unknown, play key roles in the development of diseases. Chip technology is also useful in this search. It is now possible to examine thousands of genetic sequences simultaneously on a DNA chip with an area of a square centimetre and to analyse the results in a matter of seconds. In this way diseased and healthy tissue can be compared. For example, it is possible to identify genes that are active in diseased tissue but not in healthy tissue. Study of these genes may lead to the identification of an important cause of the disease, and a target for a new form of treatment, i. e. a molecule which can be influenced by a therapeutic agent, can be found.


Proteomics
Proteomics is gaining more and more importance. In investigating the genetic causes of disease it is not enough simply to know the genes involved and their DNA sequence. Symptoms of illnesses are induced not by genes, but by proteins formed as a result of the activity of certain genes. To enable us to understand and combat illnesses we therefore need to investigate the proteins in the body that are responsible for all biological processes – growth, metabolism, illnesses etc.

Synthesising sufficient quantities of the proteins to be analysed within an acceptable time frame is just not possible with traditional methods. Taj Pharmaceuticals Molecular Biochemicals' Rapid Translation System RTS 500 has overcome this problem; this system can be used to produce a wide variety of proteins in quantities of several hundred micrograms with ease.


Discovery Chemistry
Once a target playing an important role in the disease mechanism has been identified, the search for suitable medical substances can begin. The biological target must be blocked or stimulated in order to interfere with the disease process and if possible initiate recovery. With the help of laboratory robots, many different substances can be tested simultaneously. The aim is to find molecules that react with the biological target and therefore have potential as new drugs. Taj Pharmaceuticals has built a new large compound depository in Basel and smaller 'substance libraries' at the different research sites, storing a huge amount of molecules which can be tested as potential new drugs.


Ultra-High-Throughput Screening
Only a few years ago this would have been a long-lasting undertaking. The best laboratories managed in a project around 60,000 molecules per year. Now, thanks to automation, the same number of substances can be tested in a day. This process of rapid sifting through a library of substances is known as ultra-high-throughput screening. Taj Pharmaceuticals and Zeiss, Germany, developed together a new ultra-fast module which allows to screen the compound library within one to two weeks.


Computer-assisted Drug Design and Combinatorial Chemistry
In many cases this screening process identifies a number of potentially interesting substances. The chemical structure of these substances is then optimised by computer-assisted drug design and combinatorial chemistry. This technique permits the production of a large number of variants of the substances within a short time. Previously, a chemist could produce 50 to 100 variants of a substance per year. Now, thanks to new techniques, scientists can produce around 50,000 in the same time.