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Glue2Degrade SIGNED

Therapeutic hijacking of E3 Ligases

Total Cost €

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EC-Contrib. €

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Partnership

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 Glue2Degrade project word cloud

Explore the words cloud of the Glue2Degrade project. It provides you a very rough idea of what is the project "Glue2Degrade" about.

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Project "Glue2Degrade" data sheet

The following table provides information about the project.

Coordinator
CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH 

Organization address
address: LAZARETTGASSE 14 AKH BT 25.3
city: WIEN
postcode: 1090
website: http://www.oeaw.ac.at/

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 Austria [AT]
 Total cost 1˙331˙340 €
 EC max contribution 1˙331˙340 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-STG
 Funding Scheme ERC-STG
 Starting year 2020
 Duration (year-month-day) from 2020-01-01   to  2024-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH AT (WIEN) coordinator 1˙331˙340.00

Map

 Project objective

Traditional drug design relies on inhibition of enzymes or receptors with accessible hydrophobic pockets. The concept of proteolysis targeting chimeras (PROTACs) promised to overcome this limitation. Following our discovery of the first PROTAC that induced selective protein degradation in vivo, this technology has seen a boost in academia and industry. Despite global research efforts, advances are so far incremental: (i) most focus is on degrading targets that can be liganded and are druggable with conventional inhibitors; (ii) currently, only 3 out of 600 E3 ligases can be exploited. Glue2Degrade aims to transform the pharmacologically targetable space of the proteome. The project is built on the hypothesis that molecular glues (MGs), non-chimeric small molecules that degrade target proteins by inducing cooperative binding to E3 ligases, are much more prevalent than anticipated. Lenalidomide and related immunomodulatory drugs (IMiDs) are prime examples of the potential of MGs. Without a specific targeting moiety, IMiDs induce cooperative binding of the E3 ligase CRBN to undruggable proteins like IKZF1/3, thereby inducing their degradation. However, no technologies exist to rationally develop MGs that hijack other E3 ligases. ERC-funding would allow us to address this limitation. Based on data generated in my laboratory, we will systematically identify novel MGs and their E3 ligases by innovating (i) phenotypic discovery strategies, and (ii) an orthogonal chemical genetics pipeline. To elucidate the mechanisms of novel MGs, we will (iii) conduct target identification via unbiased proteomics followed by (iv) chemical optimization and initial translational characterization. Glue2Degrade, if successful, will transform the engageable E3 space and identify novel MGs, thereby opening up the potential for therapeutic development of cell-, tissue-, and cancer-type specific chemical degraders for undruggable proteins.

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The information about "GLUE2DEGRADE" are provided by the European Opendata Portal: CORDIS opendata.

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