Development of selective protein kinase inhibitors
Jonathan Gries, Erik Schmidt, Dominik Engelskircher
Protein kinases are enzymes that physiologically play a central role in signal transduction in the human body.
They activate or inactivate other proteins via phosphorylation reactions and thereby control a variety of cellular processes.
For example, protein kinases are involved in cell growth, cell division or apoptosis.
A mutation or overexpression of protein kinases is associated with the pathogenesis of tumor diseases, among other things.
The knowledge gained over the last few decades about the underlying molecular processes now enables targeted drug targeting.
Protein kinase inhibitors work by selectively inhibiting the kinases involved in tumorigenesis and can thus curb the growth and spread of cancer cells.
In addition to their use in cancer treatment, protein kinase inhibitors are also being researched for other diseases such as inflammation, autoimmune diseases or Alzheimer's.
Our working group specializes in the following target structures:
Targeted tumor therapeutics:
- Cyclin-dependent kinase 1 (CDK1)
- Dual specific protein kinase CLK 4
- human epidermal growth factor receptor 2 (HER2)
Alzheimer's therapeutics:
- Cyclin-dependent kinase 1 (CDK1)
- Glycogen synthase kinase 3 (GSK-3ß)
- Tyrosine kinase Fyn
Literature: K. Brachwitz et al., J. Med. Chem. 46, 876-879 (2003);
B. Voigt et al., ChemMedChem 3, 120-126 (2008);
A. Opitz et al., Future Med. Chem. 3, 120-126 (2022).
Project approvals
Approval of the DFG project:
Selective protein kinase inhibitors as active substances against neurodegeneration (HI 687/8-1) as a joint project with the Medical Chemistry Group at the Institute of Pharmacy at MLU (Prof. Dr. Wolfgang Sippl) and the Paul Flechsig Institute for Brain Research at the University of Leipzig (PD Dr. Max Holzer)
Approval of the BMBF project:
Target validation: Brk as a target structure for dual targeting of advanced and metastatic breast cancer - bright2fight - Sub-project: Qualification of selective Brk inhibitors as a joint project with the Department of Clinical Pharmacy of the Institute of Pharmacy at the University of Greifswald (Prof. Dr. Christoph Ritter) and the Institute of Pharmacology and Toxicology at the University of Rostock (Prof. Dr. Burkhard Hinz)