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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.

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

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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