Targeted protein degradation in cancer therapy
A major goal of modern medicine is the development of tools that can selectively target cancer cells. Acute myeloid leukemia (AML) is an aggressive blood cancer of the myeloid cells causing bone marrow failure. The high concentrations of drugs inhibiting the activity of proteins promoting cell proliferation often lead to off-target effects. Recently, the technique that employs proteolysis targeting chimeras (PROTACs) showed promising therapeutic effects by the degradation of disease-causing proteins. The EU-funded RECOBIN-PROTACs project proposes a novel rational design and synthesis of reversible covalently binding PROTACs based on proximity labelling. A RECOBIN-PROTAC molecule consists of a target protein ligand, an E3 ligase ligand and a chemoselective functional group connected through flexible linkers selectively releasing the active RECOBIN-PROTAC inside the target cells upon protease cleavage.
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