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RGD-Diabetes SIGNED

Development of RGD-therapeutics for cardio-metabolic disease

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 RGD-Diabetes project word cloud

Explore the words cloud of the RGD-Diabetes project. It provides you a very rough idea of what is the project "RGD-Diabetes" about.

me    mediated    pressure    electrostatic    molecules    throughput    subsequently    industry    reduce    islets    translation    58       progressed    library    igf    atherosclerosis    idea    predicted    small    consistently    structures    36    lowering    matching    cell    secretion    agonists    screening    morbidity    alpha    interaction    cells    analogues    repair    domain    profiling    bind    macrovascular    commonest    skeletal    igfbp1    rgd    vitro    starting    quality    first    schemes    designing    ligands    risk    disease    innovation    million    grant    commercially    commercialisation    binding    proof    circulating    virtual    carry    diabetes    glucose    events    living    pharmaceutical    validate    possesses    amelioration    protein    vivo    hits    integrin    mortality    intolerance    stimulated    pipeline    surface    molecule    anticipate    silico    discovery    muscle    insulin    people    therapeutics    therapeutically    drug    therapies    vascular    ectodomain    hence    blood    shape    sensitisation    cardiovascular    failed    too    beta    adme    pancreatic    mimics    therapeutic    exploited    receptors    contingency    discovered   

Project "RGD-Diabetes" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY OF LEEDS 

Organization address
address: WOODHOUSE LANE
city: LEEDS
postcode: LS2 9JT
website: www.leeds.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 150˙000 €
 EC max contribution 150˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-PoC
 Funding Scheme ERC-POC
 Starting year 2019
 Duration (year-month-day) from 2019-12-01   to  2021-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY OF LEEDS UK (LEEDS) coordinator 150˙000.00

Map

 Project objective

In Europe, 58 million people are living with type 2 diabetes and 36 million people are at risk of developing the condition. Macrovascular disease is the commonest cause of morbidity and mortality in type 2 diabetes, yet current diabetes therapies have failed to consistently reduce cardiovascular events. In my Starting Grant, I discovered that a circulating protein, IGF binding protein-1, possesses several favourable characteristics– including insulin sensitisation, amelioration of glucose intolerance, blood pressure lowering, reduced atherosclerosis and increased vascular repair. These effects are mediated by interaction of the protein’s RGD-domain with cell-surface α5β1 integrin receptors, which increases insulin-stimulated glucose uptake in skeletal muscle cells and glucose-stimulated insulin secretion in pancreatic islets. Hence the ‘idea’ from my Starting Grant is that RGD-integrin interaction could be exploited therapeutically in diabetes. In this Proof-of-Concept grant, we will take the first step towards commercialisation of the idea by designing and testing small molecule mimics of the RGD domain of IGFBP1 as diabetes therapeutics. Using in silico modelling based on the known structures of IGFBP1 and the α5β1 integrin ectodomain, we will design a small molecule library of commercially available potential agonists. We will carry out virtual high throughput screening of the library for molecules matching the shape and electrostatic potential of the RGD domain of IGFBP1 as predicted to bind to α5β1 integrin. As contingency, we will also identify in silico ‘me-too’ analogues of known integrin ligands. We will test the best quality hits through ADME profiling and validate therapeutic activity in vitro and in vivo. At the end of the project, we anticipate we will have identified small molecule RGD mimics which can subsequently be progressed through the drug-discovery pipeline through translation grant funding or pharmaceutical industry Open Innovation schemes.

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lastchecktime (2022-12-09 8:49:06) correctly updated