ACKLE is a collaborative research project involving the University of Milan, Charles University, and the University of Warsaw. Its main goal is to develop novel small molecule-protein degraders (PROTACs) targeting Aldo-Keto Reductase isoforms, primarily AKR1B10, in order to overcome anthracycline resistance in cancer. The project combines computational modeling, medicinal chemistry, and biological validation in a highly integrated workflow. The University of Warsaw will lead the in silico design and prioritization of candidate degraders, the University of Milan will carry out the synthesis and analytical characterization of the selected compounds, and Charles University will perform the biological evaluation in relevant cancer models. Overall, TACKLE aims to generate proof-of-concept evidence for a new degradation-based therapeutic strategy against drug-resistant cancers.
The expected outcomes include computational models of PROTAC-AKR interactions, a small set of synthesized and fully characterized candidate degraders, and preliminary biological data on AKR1B10 binding, degradation, and the restoration of anthracycline sensitivity in cancer cells. More broadly, the project is expected to strengthen interdisciplinary collaboration within the 4EU+ Alliance, support the training of early-career researchers, and provide a solid basis for future national and European grant applications.
carlo.matera@unimi.it
Carlo Matera is Associate Professor of Medicinal Chemistry at the University of Milan, where he conducts research on the design and development of bioactive small molecules for biomedical applications (https://iamc.unimi.it/). His expertise includes synthetic medicinal chemistry, compound optimization, and analytical characterization. Within the TACKLE project, he serves as project leader and coordinates the consortium’s research activities, with a specific focus on the development of targeted protein degraders aimed at overcoming anthracycline resistance in cancer.