Searching systematically for active agents
Scientists test thousands of substances in their hunt for new medicines. Chemist Michael Haerter developed software that analyzes these large-scale experiments. Today, this software plays a key role in the hunt for new active agents.
In chemistry, ideas and concepts materialize in new substances – a transformation that has fascinated me since I was as a student. Today, I’m happy that this fascination is part of my work in pharmaceutical research at Bayer. For me, it all centers around one creative moment: when I generate new ideas for better molecules by connecting chemical structural fragments with pharmacological attributes. In a second step, I synthesize these molecules, and imagined and desired characteristics can hopefully move from an idea into reality.
Most of my tests in the lab do not lead to the ultimate goal: finding a new active agent that brings a patient relief, or even a cure from the disease itself. If this outcome bothered me, I would have had to give up during my university studies in chemistry. Failures are a part of a chemist’s daily routine, so they’re a part of my job. Working for Bayer in Wuppertal, Germany, I search for potential active agents to fight diseases, so I produce them chemically and then test them. Currently, I’m working with potential agents for lung conditions.
Failure brings progress
Those who understand how we chemists work can also understand why our efforts often go wrong – and that this ‘failure’ still helps our research get further. There are more than four million substances stored in Bayer’s substance library that provide me and my team with a great source of research material. Each one of these substances can be chemically modified in thousands of ways. So there are billions of candidates that could be synthesized in our quest for the right molecule to treat a specific disease.
When I started working for Bayer in 1997, the trend was to synthesize and test these substances in large numbers. With automated lab equipment, thousands of these experiments could be conducted within days. This approach, however, was less successful than we had expected when it came to optimizing a molecule’s properties. We learned that we had to combine large-scale testing with a strategy, and with more knowledge about these substances.
Utilizing ‘Big Data’ – first
In 1999, a handful of colleagues and I started a project. We wanted to systematize the search for and optimize active agents with the help of computers and databases. That’s why I have to smile sometimes when I hear an expert today talking about this ‘new’ trend called ‘Big Data’. We basically used the same thing back then, only without using that term. We developed software that plays a key role in researching active agents at Bayer.
Today, and thanks to this software, I have fast access to all the data I need for my work. This data is fed by the test labs into a common digital database – often, this process is even automated. It wasn’t like that back when we started. And our software helps to correlate chemical structures with biological phenomena – and visualizes the results quickly. Now we can develop hypotheses about the way we have to modify a molecule to reach a desired effect. This ability has greatly advanced our research.
CV Dr. Michael Haerter
|1966||Born in Cologne, Germany|
|1987 – 1992||Chemistry studies at the University of Cologne|
|1992||Diploma (combined BS and MS) in Chemistry|
|1992 – 1995||PhD at the University of Cologne (Dr. rer. nat.; Doctor of Natural Sciences), Physical Organic Chemistry
PhD fellowship award from the Fonds des Verbandes der chemischen Industrie (FCI)
|1995 – 1997||Postdoctoral studies at The Scripps Research Institute, San Diego, California, USA. Focus: synthesis of complex naturally occurring substances
Sponsored by a scholarship from the Studienstiftung des deutschen Volkes (BASF program)
|1997 - current||Laboratory Head in medicinal chemistry of pharmaceutical research, Bayer, Wuppertal, Germany|
|2004 - current||Principal Research Scientist|
Inhibition of hypoxia-induced gene transcription by substituted Pyrazolyl oxadiazoles: Initial lead generation and structure-activity relationships.
M. Härter, K.-H. Thierauch, S. Boyer, A. Bhargava, et. al., ChemMedChem 2014, 9 (1), 61-66
Estimation of Physicochemical and ADME Parameters.Inhibition of hypoxia-induced gene transcription by substituted Pyrazolyl oxadiazoles: Initial lead generation and structure-activity relationships.
M. Härter, K.-H. Thierauch, S. Boyer, A. Bhargava, et. al., ChemMedChem 2014, 9 (1), 61-66:M. Härter, J. Keldenich, W. Schmitt, Handbook of Combinatorial Chemistry Volume 2 (K. C. Nicolaou, R. Hanko, W. Hartwig, edts.), Wiley-VCH, Weinheim 2002
Heterocyclylmethyl-thienouracile as antagonists of adenosine-A2B receptor and their preparation.
WO 2016150901 A1
M. Härter, D. Kosemund, M. Delbeck, B. Kalthof, et. al.,
Preparation of cyclic thienouracil-carboxamides useful as A2b receptor antagonists.
WO 2015052065 A1
M. Härter, M. Delbeck, B. Kalthof, K. Lustig et. al.
Bayer AG, 2013: Preparation of 3-(fluorovinyl)pyrazoles and use thereof in the treatment of hyperproliferative and angiogenic diseases.
WO 2013011033 A1
M. Härter, H. Beck, K.-H. Thierauch, P. Ellinghaus, et. al.
Preparation of substituted oxadiazolyl pyridinones and oxadiazolyl pyridazinones as HIF inhibitors.
WO 2013057101 A1
M. Härter, H. Beck, P. Ellinghaus, K. Unterschemmann
2010: Otto Bayer Medal for developing a central digital platform that combines all available data and applications and that helps scientists making decisions in the complex area of chemical and biological data