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CHANCE

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Structure guided inhibition of IDOL to treat atherosclerosis and the metabolic s...

Structure guided inhibition of IDOL to treat atherosclerosis and the metabolic syndrome The prevalence of the MetS and associated co-morbidities including cardiovascular disease has reached epidemic proportions in the developed and developing world. The cost of treating these conditions represents a substantial part... ver más

31/03/2022

Academisch Medisch...

150K€

Presupuesto del proyecto: 150K€

Líder del proyecto

Academisch Medisch Centrum AMC No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Ver 2 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2022-03-31

ERC-2019-POC: ERC Proof of Concept Grant

I+D

Cerrada hace 5 años

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2 Participantes

Academisch Medisch Centrum A...

150.00K€ | Lider

INGABSA CONSULTORES SL EN LI...

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Duración del proyecto: 30 meses Fecha Inicio: 2019-09-02
Fecha Fin: 2022-03-31

Líder del proyecto

Academisch Medisch Centrum AMC No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 150K€

Descripción del proyecto The prevalence of the MetS and associated co-morbidities including cardiovascular disease has reached epidemic proportions in the developed and developing world. The cost of treating these conditions represents a substantial part of current European healthcare expenditure, and despite recent advances, treatments for MetS-associated lipid disorders are far from optimal; mainstay lipid-lowering treatments (e.g. statins) reduce cardiovascular risk by only ~30%, and recently-introduced PCSK9 inhibitors are promising, but prohibitively expensive. Moreover, epidemiologic and genetic evidence suggests that these treatment modalities are associated with a significant increase in the risk for development of diabetes. Treatments for other MetS-associated comorbidities, including dyslipidemia, diabetes, obesity, and fatty-liver disease are far from optimal or lacking. In ERC-CoG UNICOM we discovered that genetic inhibition of the E3-ubiquitin ligase IDOL protects mice from the detrimental development of multiple MetS-associated comorbidities. We therefore propose IDOL inhibition as a novel therapeutic strategy to concomitantly target multiple metabolic co-morbidities. However, absence of a high resolution IDOL structure has hampered structure-guided development of inhibitors. In CHANCE, we will capitalize on the high resolution 3D structure of IDOL that we recently obtained. Using this unique structure we aim to identify and validate small-molecule IDOL inhibitors by using a structure-guided development pipeline that combines an established virtual ligand docking protocol, and in vitro and in vivo validation. Lead hits will be used for development of a business and IP strategy to ensure the sustainable development of IDOL inhibitors for treating the MetS.

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