Objective
Protein-protein interactions are central elements in cellular processes and important targets for selective therapeutic agents. They constitute a rich area for discovery of novel small ligand-based therapies.This proposal seeks to utilise such interactions, in particular those featuring an alpha-helix binding groove, such as p53-MDM2, or more novel targets e.g. n23-prune to develop targeted small molecule libraries with physico-chemical properties appropriate for therapeutic effect against various tumour types such as the brain cancers of glioblastoma and medulloblastoma. Combination of the concepts below should provide an opportunity to unlock the potential of protein interactions as key components in signalling pathways via design of selective small molecule modulators targeting the kinase-effector interaction instead of the ATP active site.Data-mining of ADME and drug-drug interactions to build a predictive database for library design.
Develop quantitative structure/property relationships, with an emphasis on CYP-mediated metabolism,ABC transporters at the blood/brain and brain/tumour interfaces,mutagenicity, solubility, pKa,and passive permeability,and predictive tools for mutagenicity and other genetic toxicology end-points.Develop predictive PK and PBPK models to improve understanding of BBB and tumour penetration.In vitro and in vivo PK/PD and TK/TD characterisation of compounds, to increase understanding of their mechanism of action and reduced the use of laboratory animals.Develop an understanding of the elements controlling selectivity in protein-protein signalling networks by developing approaches for design of small molecules that target alpha-helix binding groove interactions through use of structure based and fragment based approaches. Such knowledge-based approaches will also be applicable to the design of small molecules for other protein-protein interactions that utilize an alpha-helix binding groove and for other therapeutic areas.
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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences computer and information sciences databases
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine toxicology
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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.
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.
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.
FP6-2005-LIFESCIHEALTH-7
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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.
Coordinator
SIENA
Italy
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.