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Targeting Type 2 Diabetes with Allene-containing Molecules Using a C-N Bond Cleavage Tool

Project description

C-N bond cleavage for safer type-2 diabetes therapy

Type 2 diabetes affects over 450 million people worldwide. Key treatment targets include peroxisome proliferator-activated receptors (PPARs) and G-protein-coupled receptors (GPCRs), specifically free fatty acid receptors (FFARs). However, the phase III trials of GPR40 agonists were halted due to liver toxicity concerns. The ERC-funded ALLENEDRUG project will focus on developing new GPR40 ligands to provide safer therapies for type 2 diabetes. Using a synthetic approach, the project will create enantiomerically enriched allenes through selective C-N bond cleavage. These compounds will be tested as potential GPR40 agonists, and their structure-activity relationship (SAR) in relation to liver toxicity will be carefully evaluated, with comparisons made to molecules currently undergoing phase III clinical trials.

Objective

Type 2 Diabetes is a chronic disease affecting more than 450 million people world-wide and is still an unmet medical need. PPAR´s
(Peroxisome Proliferator-Activated Receptors) and G-protein-coupled receptors (GPCR) FFARs (Free Fatty Acid Receptors) are well
clinical validated targets for type-2 diabetes. Although selective GPR40 agonists have reached clinical phase III, the trials were
recently terminated due to signs of liver toxicity in patients. ALLENEDRUG is designed to provide a new chemical series of GPR40
ligands aiming to bring a safer type-2 diabetes therapy. To achieve this goal, we will use a synthetic tool developed in our laboratory
to prepare enantiomerically enriched allenes through a selective C-N bond cleavage. This ERC-PoC will allow us to test the new
chemical series as potential GPR40 agonists and to get insight into a SAR (Structure Activity Relationship) correlation with liver toxicity
in order to compare the new molecules prepared in this proposal with those currently in clinical phase III trials.

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2024-POC

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Host institution

UNIVERSIDAD AUTONOMA DE MADRID
Net EU contribution

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.

€ 150 000,00
Address
CALLE EINSTEIN 3 CIUDAD UNIV CANTOBLANCO RECTORADO
28049 MADRID
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Higher or Secondary Education Establishments
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Total cost

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Beneficiaries (1)

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