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leadXpro “unlocks” new targets for structure-based drug discovery

The structure of only 30 out of 800 known human membrane proteins is currently defined and can be used in structure-based drug dicovery.
The structure of only 30 out of 800 known human membrane proteins is currently defined and can be used in structure-based drug dicovery.

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One of the most promising groups of drug targets is that of integral membrane proteins. They are responsible for communicating signals from the outside to the inside of the cell. When the medicinal chemists know proteins’ structure, they can easier identify the right compounds that will bind with high affinity. This process is called structure-based drug discovery.

The structure of only 30 out of 800 known human membrane proteins is currently defined and can be used in structure-based drug discovery. At PARK INNOVAARE, leadXpro AG is committed to unlocking more membrane protein targets for modern drug discovery efforts by mastering the generation of purified proteins, applying biophysical methods and fully utilizing the Paul Scherrer Institute PSI facilities such as the Swiss Light Source (SLS) and Free-Electron Laser (SwissFEL). Founded in December 2015, leadXpro AG is one of the first high-tech companies to be located at PARK INNOVAARE. It was of the highest importance for its founders, Professor Dr. Michael Hennig, Professor Dr. Gebhard Schertler and Dr. Rafael Abela, to set up the young biotech company in close proximity to the Paul Scherrer Institute PSI and its unique research facilities.

Novel methods and technologies for structure identification

Focusing on integral membrane proteins that are responsible for key disease-related mechanisms in humans, leadXpro enables the discovery of new medicines by applying biophysical methods. Such methods include X-ray crystallography, single-particle cryo-electron microscopy and other ligand-binding methods for identifying and analyzing the molecular interaction of potential new drug molecules with the target protein, facilitating the discovery and optimization of lead compounds. Among other things, the unique set of large research facilities at PSI (SLS and the newly launched SwissFEL) allows for serial crystallography. It enables scientists to determine the structure of drug complexes with receptors at more physiological room temperature compared to the cryo-crystallography of the past.

The expertise of the leadXpro team is in generating purified protein in a disease-relevant activity. Combined with the close partnership with the state-of-the-art equipment and research facilities of PSI, it allows the company to identify new lead compounds with unprecedented specificity and efficacy, uncovering new allosteric mechanisms of action, and to unravel challenging binding sites.

Better cancer treatment and antibiotics

Apart from the services provided to the pharmaceutical industry, leadXpro’s own research activities are focused on lead discovery and optimization for better cancer treatments, through the understanding of selected pathways linked to immunomodulatory and inflammatory mechanisms. In addition, leadXpro strives to identify antibiotics with new mechanisms of action: “Many bacteria have developed resistance to existing, well-known antibiotics. Combining or increasing dose therapies will buy time, but not solve the problem. We want to use new target molecules, for example from the outer membrane of Gram-negative bacteria, to enable the development of new treatment options,” explains Professor Michael Hennig, CEO of leadXpro.

After only one year in operation, leadXpro has already shown first results. Apart from strategic collaborations with the PSI and the University of Basel for technology teamwork, contracts have been signed with a number of pharmaceutical companies. The company has ambitious plans for 2017: extension of the lab and office space, new projects and collaborations with pharmaceutical companies and team growth. Just this February, three more highly qualified colleagues joined the team of now seven specialists.