Department of Drug Design and Target Validation

To protect the population from future pandemics, it is essential to focus on the development of new technologies for the treatment or prevention of viral and bacterial infections. The Drug Design and Target Validation branch of the Fraunhofer Institute for Cell Therapy and Immunology (IZI) develops new molecular strategies for the treatment and prevention of infectious diseases. Furthermore, the institute supports regional SMEs and international large companies in the fields of biotechnology and pharmaceuticals in the development of antiviral agents, antibiotics, and vaccines through a wide range of expertise in all preclinical and clinical development phases.

Through the close networking of active substance and structural biology, analytics, antibody technologies, and pharmacology, new treatment concepts are developed at Fraunhofer IZI using both "small molecules" and biological agents ("biologicals") and are tested in living organisms (in vivo) for efficacy and tolerance. However, the identification, characterization, and formulation of promising active substance candidates in the context of preclinical and clinical developments requires extensive investigation of these molecules regarding their chemical and biophysical properties. This allows for a much better understanding of pharmacological properties to identify points for further improvements.

A key element of the infrastructure measure is the expansion of the equipment portfolio with state-of-the-art analytical instruments from the fields of calorimetry, spectroscopy, liquid chromatography, and mass spectrometry. The techniques have been used for decades for the identification, characterization, and quantification of active ingredients and active ingredient candidates. They are indispensable for the development and (clinical) testing of new drugs, as they offer the possibility of correlating the molecular properties of the active substance with its effect in the organism. The use of AI for the evaluation of mass spectrometric datasets not only facilitates their interpretation but also enables a deeper analysis, providing new insights into molecular relationships crucial for active substance development.

In addition, the instruments will be integrated into the GLP testing facility of Fraunhofer IZI, ensuring seamless use of the generated research data for clinical development. The infrastructure measure enables the accelerated development of new antibacterial and antiviral agents in cooperation with biotechnology and pharmaceutical companies.

Sun exposure is essential for human health; however, the phototoxic effects of excessive UVB and UVA radiation, which can lead to sunburn, skin aging, and even tumor formation, are well known and extensively researched. Sunscreens are one of the most important means of protecting the skin from UV-related phototoxic damage. In addition to synthetic agents for skin protection, natural substances are increasingly coming into focus in development, considering environmental and biocompatibility aspects.

The aim of the project is to investigate and develop new strategies for the prevention of UV light-induced skin damage based on the plant constituents of several lady's mantle species.

The Fraunhofer IZI contributes its expertise in molecular drug research and therapy development. Through biological assays, in vitro models, and a comprehensive pharmacological characterization of selected plant extracts, their photoprotective activity, anti-inflammatory potential, and effects on collagen metabolism, proliferation, and differentiation of skin cells will be specifically investigated.

As a result, promising extracts and active substances will be identified and preclinically evaluated to prepare suitable candidates for clinical development.

Project partner
Partner: Medicos Science Center GmbH in Bernburg

Neurodegenerative diseases, particularly Alzheimer's, present indications associated with a chronically progressive loss of neurons. Although numerous risk factors and also strategies to prevent neurodegeneration are already being tested, drug intervention is not usually an option. Recent studies have further highlighted a correlation between infections and neurological functional disorders. A connection with the emergence of neurodegeneration cannot be ruled out.

The Department of Drug Design and Target Validation at Fraunhofer IZI is focused in particular on carrying out research into these diseases and investigating potential therapeutic molecules. Building on this, new treatment concepts that draw on small molecules and biologicals will be developed and investigated as to their efficacy and tolerability in the living organism. The department boasts a wealth of experience stretching back many years in the preclinical development of drugs, with expertise covering practically the entire range of tasks associated with preclinical drug development.

Investigating, developing and optimizing promising drug candidates does however require a thorough examination of these molecules at their sites of action in the protein (targets) in order to understand modes of action and identify where improvements could be made. This is where structure determination comes in: Using X-ray crystallography, a three-dimensional image can be obtained of drug molecules bound to their site of action. In addition, testing drug candidates in vitro and in vivo requires an extensive analysis of their purity and of the kinetic binding behavior at the site of action by means of mass spectrometry and other biophysical methods, e.g. SPR or ITC.

By providing this infrastructure, it will be possible in Halle (Saale) to characterize new and known drugs in detail in future with regard to their mode of action and to optimize them accordingly.

Project manager: Prof. Dr. Stephan Schilling