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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.

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

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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