Bach Group – University of Copenhagen

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Department of Drug Design and Pharmacology > Research > Medicinal Chemistry Research > Chemistry and Medicinal Chemistry > Bach Group

Bach Group

 

In our group we develop biological active small-molecule inhibitors against key CNS proteins involved in excitotoxicity and oxidative stress. We evaluate the druggability of selected targets and aim at developing new high-quality chemical probes useful for pharmacological studies and for identifying new therapeutic principles against ischemic stroke and related diseases.

Fragment-based drug discovery (FBDD) is a core theme of our research. We screen our library of >2500 fragments (small substructures of drug like molecules) using biochemical and sensitive biophysical methods, such as SPR and ligand-based NMR. Promising hits are optimized into lead molecules by medicinal chemistry, biostructural studies and pharmacology.

Another theme of our research is to develop multi-target inhibitors, which are likely to provide greater effects against complex diseases, such as ischemic stroke. We hope that FBDD can be used as a tool to directly search for multi-target hits, which can then be optimized into larger and more efficient multi-target inhibitors.

Research projects

  • Keap1

    Keap1’s Kelch-DC domain interacts with Nrf2. Inhibition of this protein-protein interaction leads to Nrf2 nucleus translocation and transcription of antioxidant genes and thus cellular protection.

  • NADPH Oxidase

    NADPH oxidase is a superoxide-producing membrane-bound enzyme complex. Compounds targeting the SH3 domains of p47 can prevent assembling of the complex and lead to less toxicity.

  • PSD-95

    PSD-95 binds the NMDA receptor and nNOS. Compounds targeting PDZ1-2 of PSD-95 disrupt this ternary protein complex and lead to less excitotoxicity-mediated nitric oxide and thus cell protection.