Objective
Classical drug design relies mostly on the availability of accessible pockets to block specific protein activities. Despite tremendous progress, more than 80% of all human proteins remain beyond the reach of traditional inhibitor-centric approaches. Chemical ablation of protein abundance using bivalent degraders (PROTACs) moves away from an occupancy-driven (inhibition) to an event-driven (binding) pharmacology. However, their design is intrinsically limited to targets that are ligandable via chemical probes. To tackle current unmet clinical problems, we need transformative paradigms.
Fortuitous discoveries have illustrated the immense potential of monovalent degraders. These molecules induce the degradation of target proteins by molecular gluing to E3 ubiquitin ligases or by prompting their destabilization. They have desirable drug-like properties, proven capacity to induce the degradation of proteins otherwise deemed undruggable, and they are already a clinical reality. However, their discovery has been driven by serendipity, thereby hampering their realization as a generalizable drug solution.
TrickE3 seeks to establish the foundations for the systematic development of monovalent degraders. To this end, we will develop innovative methodologies to detect and predict drug-induced changes in the interactome/activity of E3s at scale. As proof of principle, we will focus on the chemical rewiring of E3s expressed in pancreatic ductal adenocarcinoma (PDAC) due to the imperative need for treatments. We intend to prospectively identify monovalent degraders (i) of specific vulnerabilities, and (ii) to unlock new PDAC targets.
At the interface of chemical biology and cancer research, TrickE3 will be an instrumental resource to broaden drug discovery efforts, probe disease-relevant vulnerabilities and, overall, widen the targetable space of the human proteome. We hope to empower other disciplines to chemically explore, without limits, the degradation of relevant targets.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine oncology prostate cancer
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences basic medicine pharmacology and pharmacy
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2021-STG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
08028 BARCELONA
Spain
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.