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UA Ruhr Researchers Jointly Develop Basis for Targeted Cancer Therapy

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Different molecules are presented © Archiv​/​TU Dort­mund
The figure shows the active substance borussertib (blue) in complex with the dysregulated protein molecule AKT (white and green). The active substance fits like a key into the lock of the protein molecule and thus blocks its function.

From basic research to application – the way to drug discovery is long. Scientists from TU Dort­mund University, the Medical Faculty of the University of Duisburg-Essen at the West German Cancer Centre Essen and Ruhr-Uni­ver­si­tät Bochum have joined forces and have now produced and tested a potential active substance. With great success: The so-called “covalent-allosteric AKT inhibitor borussertib” has shown a promising effect against pancreatic cancer. The results were recently published in the renowned journal Cancer Research.

“This success could only be achieved through the cooperation of the various partners,” said Daniel Rauh, Professor of Medicinal Chemistry and Chemical Biology at TU Dort­mund University, adding that “in a few years’ time, the new active substance could become an effective drug.” Due to its aggressiveness and high resistance, pancreatic cancer has unfortunately thus far proven to be insufficiently treatable. This is the starting point of Rauh’s research: By means of computer modeling, he and his team developed the new inhibitor, which is designed to disrupt the functioning of cancer cells. “Explained in a simple analogy, if you remove the spark plugs from a car, it won’t start anymore. The same applies to the tumor cell,” said Rauh, “its functioning is specifically disturbed.”

Success through collaboration within the University Alliance Ruhr

Designing and manufacturing the new active substance was a great success in itself. However, to make further progress, the chemists and structural biologists from Dort­mund sought support from other researchers. In order to test the potential active substance, they worked together with physicians from Essen and Bochum: Professor Jens Siveke from the West German Cancer Centre at Essen University Hospital is an expert on pancreatic cancer; Professor Stephan Hahn and his team at Ruhr-Uni­ver­si­tät Bochum were able to test the active substance in vivo. For the first time, the effect observed initially only in cancer cell models could also be demonstrated in the living system, in this case in mice. By the way, the researchers chose the name of the new active substance, borussertib, as a reference to their favorite football club.

New insights into the effect of the inhibitor

Another success of the collaboration: The team was able to visualize the crystal structure of the disease-causing cells three-dimensionally for the first time. Professor Rauh explained what this means: “Imagine a lock and a key. If I know exactly what the lock looks like and how it works, I can make a suitable key for it.” In this case, the lock is a dysregulated protein molecule and the key is the new active substance. “In this way, we have gained valuable insights into the mechanism of action of the inhibitor at the atomic level,” said Rauh. The focus of further research is now on optimizing the new active substance in order to further develop it for clinical testing. This work will be carried out at the Drug Discovery Hub Dort­mund (DDHD).

The joint research was funded by the Mercator Research Center Ruhr (MERCUR) and supported by the Lead Discovery Center GmbH and IfADo – Leibniz Research Centre for Working Environment and Human Factors in Dort­mund. MERCUR promotes cooperation between Ruhr-Uni­ver­si­tät Bochum, TU Dort­mund University and the University of Duisburg-Essen, which have been working closely together since 2007 under the umbrella of the University Alliance Ruhr (UA Ruhr).

Under the motto “Better Together”, Ruhr-Uni­ver­si­tät Bochum, TU Dort­mund University and the University of Duisburg-Essen have joined together to form the University Alliance Ruhr (UA Ruhr). Since 2007, the three major universities in the Ruhr region have been pooling their expertise and thus strengthening their capabilities. More than 120,000 young people study, conduct research and work together in a network encompassing a subject spectrum ranging from engineering and natural sciences to the humanities, social sciences and medicine. The UA Ruhr thus makes the Ruhr region one of the strongest science locations in Germany.

Online version of the article in the journal “Cancer Research”

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Location & approach

The campus of TU Dort­mund University is located close to interstate junction Dort­mund West, where the Sauerlandlinie A 45 (Frankfurt-Dort­mund) crosses the Ruhrschnellweg B 1 / A 40. The best interstate exit to take from A 45 is "Dort­mund-Eichlinghofen" (closer to Campus Süd), and from B 1 / A 40 "Dort­mund-Dorstfeld" (closer to Campus Nord). Signs for the uni­ver­si­ty are located at both exits. Also, there is a new exit before you pass over the B 1-bridge leading into Dort­mund.

To get from Campus Nord to Campus Süd by car, there is the connection via Vogelpothsweg/Baroper Straße. We recommend you leave your car on one of the parking lots at Campus Nord and use the H-Bahn (suspended monorail system), which conveniently connects the two campuses.

TU Dort­mund University has its own train station ("Dort­mund Uni­ver­si­tät"). From there, suburban trains (S-Bahn) leave for Dort­mund main station ("Dort­mund Hauptbahnhof") and Düsseldorf main station via the "Düsseldorf Airport Train Station" (take S-Bahn number 1, which leaves every 20 or 30 minutes). The uni­ver­si­ty is easily reached from Bochum, Essen, Mülheim an der Ruhr and Duisburg.

You can also take the bus or subway train from Dort­mund city to the uni­ver­si­ty: From Dort­mund main station, you can take any train bound for the Station "Stadtgarten", usually lines U41, U45, U 47 and U49. At "Stadtgarten" you switch trains and get on line U42 towards "Hombruch". Look out for the Station "An der Palmweide". From the bus stop just across the road, busses bound for TU Dort­mund University leave every ten minutes (445, 447 and 462). Another option is to take the subway routes U41, U45, U47 and U49 from Dort­mund main station to the stop "Dort­mund Kampstraße". From there, take U43 or U44 to the stop "Dort­mund Wittener Straße". Switch to bus line 447 and get off at "Dort­mund Uni­ver­si­tät S".

Dort­mund Airport offers flights to several destinations in Central Europe. There are regular connections to Katowice, Kraków, London and Munich. For the approximately 20km-trip from Dort­mund Airport to TU Dort­mund University, you can use a shuttle bus to the railway Station "Bahnhof Holzwickede", from which trains depart to Dort­mund main station (please visit Verkehrsverbund Rhein-Ruhr for more in­for­mation). Normally, the fastest way is to catch a taxi at Dort­mund Airport.

The H-Bahn is one of the hallmarks of TU Dort­mund University. There are two stations on Campus Nord. One ("Dort­mund Uni­ver­si­tät S") is directly located at the suburban train stop, which connects the uni­ver­si­ty directly with the city of Dort­mund and the rest of the Ruhr Area. Also from this station, there are connections to the "Technologiepark" and (via Campus Süd) Eichlinghofen. The other station is located at the dining hall at Campus Nord and offers a direct connection to Campus Süd every five minutes.