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Design, synthesis and biological evaluation of PROteolysis-TArgeting Chimeric (PROTAC) molecules as anticancer agents

Project description

Proteolysis-targeting chimeric technology in the development of anticancer drugs

Traditional anticancer small-molecule inhibitors are a powerful resource in chemotherapy, but they often encounter problems such as drug resistance due to target alterations, ineffective apoptosis or activation of different pathways. Proteolysis-targeting chimeras (PROTACs) represent a promising approach to prevent drug resistance since they cause target degradation, reducing systemic drug exposure and other potential side effects. The chimeric molecules consist of the domain that binds to the protein targeted for degradation and the domain that binds to the E3 ubiquitination ligase. The EU-funded PROTACs project aims to design, synthesise and evaluate a series of PROTACs based small molecules for the degradation of protein targets associated with tumour development and progression.


Cancer diseases are critical medical problems - according to the International Agency for Research on Cancer and European Commission estimates, globally there were more than 18 million new cases and 9.5 million cancer-related deaths in 2018, what indicates that tumors are among the leading causes of death, worldwide.
Traditional anticancer drug design based on small molecules continues to be a powerful strategy for the development of novel chemotherapeutics. However, these anticancer therapies are facing major problems such as drug resistance, especially in advanced cancers. This is mainly due to the alterations in the target, ineffective apoptosis or activation of different pathways, among others. The use of PROteolysis-TArgeting Chimerics (PROTACs) has become a promising approach to overcome resistance since they act degrading instead of inhibiting the target, with the advantage of reducing the systemic drug exposure and to counteract the protein expression that often accompanies inhibition of protein function. This approach uses bivalent molecules that possess a target protein recruiting group linked to an E3 ligase interacting moiety for protein degradation.
The main goal of this project is to design, synthesize and evaluate a series of new small-molecule PROTACs, which will be able to degrade enzymes and receptors that are responsible for tumor development and progression. To address this aim, I shall carry out a fellowship at Universidad San Pablo CEU under the supervision of Prof. Beatriz de Pascual-Teresa and Irene Ortín from Faculty of Pharmacy. As part of this research, I shall carry out a secondment in the Department of Molecular Biotechnology and Health Sciences at University of Turin (Italy), and another one at the company CsFlowChem S.L. It is worth noting that the design and synthesis of new PROTACs will be based on our wide experience in the development of compounds responsible for inhibition or regulation of the selected target proteins.


Net EU contribution
€ 172 932,48
28040 Madrid

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Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Higher or Secondary Education Establishments
Total cost
€ 172 932,48