Talk Title: Chemical Proteomics Reveals the Target Space of Hundreds of Clinical Kinase Inhibitors
Bernhard Kuster is a chemist by training and obtained is PhD in Biochemistry from the University of Oxford. He went on to do a PostDoc funded at the EMBL in Heidelberg and the University of Southern Denmark. After seven years as VP Analytical Sciences and Informatics at the biotech firm Cellzome, he became full professor of Proteomics at the Technische Universität München in 2007 where he is also the Chair of the Department for Biosciences and Co-Director of the Bavarian Biomolecular Mass Spectrometry Center.
Bernhard’s research focuses on mass spectrometry based proteomics and its application to chemical and systems biology. He is particularly interested in how drugs interact with proteins, signaling pathways and cellular systems in order to understand how these molecules work. His team continues to develop technologies for the exploration of the human proteome and its application to drug discovery and personalized medicine.
Chemical Proteomics Reveals the Target Space of Hundreds of Clinical Kinase Inhibitors
Kinase inhibitors have developed into important cancer drugs because de-regulated protein kinases are often driving the disease. Close to 40 such molecules have been approved for use in humans and several hundred are undergoing clinical trials. As most compounds target the ATP binding pocket, drug selectivity among the 500 human kinases is a recurring question. Clinicallyspeaking, polypharmacology can be beneficial as well as detrimental. Therefore, knowing the full target spectrum of a drug is important but rarely available. We have used a quantitative chemical proteomics approach to profile 240 clinical kinase inhibitors in a dose dependent fashion in cancer cell lysates to identify thousands of drug-protein interactions. This presentation will outline how this information is generated and how it can be used to identify molecular targets of toxicity, re-purposing existing drugs for new indications, finding combinations of drugs to overcome resistance or provide starting points for new drug discovery.