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Innovative therapies for human diseases: Targeted degradation as new mode of action for drugs (ProxiDrugs)

The new class of proximity-induced drugs allows for the targeted degradation of disease-relevant proteins (target structures), opening up new therapeutic options in numerous diseases, amongst them some with high unmet medical need. The respective drugs usually are small, bifunctional molecules that direct target structures straight towards the cellular waste system. It is assumed that 80% of proteins that are so far deemed as undruggable may be targeted by this strategy. Within the Rhein-Main region, the relevant expertise needed to bring this innovative strategy to a broad application is clustered in a Europe-wide unique way. Therefore, together with Fraunhofer Institute IME and Technical University Darmstadt, Goethe University Frankfurt plans to establish the ProxiDrugs Cluster4Future. The key piece of the Cluster is a technology platform for drug discovery and preclinical development. The Cluster aims at improving the new class of drugs in different ways: The strategy comprises the identification of suitable functional subunits for molecule engineering, the directed optimization of pharmacological properties, and the transfer to clinical phases. The Cluster will especially benefit from the know-how, relevant facilities and equipment as well as available screening libraries at the Structural Genomics Consortium Frankfurt Site and at Fraunhofer IME. Numerous regional partners have already expressed an interest in concrete projects, amongst them big pharma companies as well as small spin-offs.

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NEWS

03 Feb 2021 - PROXIDRUGS successful in Clusters4Future competition

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As announced today, the PROXIDRUGS consortium has been selected for funding within the Clusters4Future initiative of the Federal Ministry of Education and Research (BMBF), which aims at promoting regional innovation networks for the benefit of economy and society. PROXIDRUGS will be funded with up to 15 M € for the next three years, as only one of 7 clusters selected for funding from a total of 137 applications. 

The consortium concentrates on developing new treatments for diseases with high unmet medical need by utilizing the new concept of proximity induction in drug design. It is assumed that 80% of the proteins that are so far deemed as undruggable may be targeted by this strategy. “Proxidrugs open up exciting new therapeutic options in numerous diseases including cancer, neurodegeneration and infection. Proxidrugs can trigger degradation of disease-relevant proteins in a highly specific fashion by directing them towards the cellular recycling system”, explains cluster speaker Ivan Đikić from Goethe University. 

PROXIDRUGS has been set up as a regional network of partners from academia and industry, covering the entire value chain from basic to translational research. Academic participants are based at Goethe University Frankfurt, TU Darmstadt, University of Heidelberg, the MPI of Biophysics and the Fraunhofer Institute for Translational Medicine and Pharmacology, and they are closely working together with major pharma partners. 

At Goethe University, the Frankfurt Center for Innovation & Technologies will be established as academic innovation hub that provides the needed technologies to the consortium. Ivan Đikić adds: “The early and close collaboration between all partners marks the start of a new era in drug development within the Rhine Main region. This culture of teamwork and sharing knowledge paves the way for an efficient transfer towards therapeutic applications.”
 

EVENTS

»Identifying fragments binding to the entire genome and proteome of SARS-CoV-2«
Joint Lecture PROXIDRUGS & ENABLE
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Prof. Dr. Harald Schwalbe
Institute for Organic Chemistry and Chemical Biology
Center for Biomolecular Magnetic Resonance (BMRZ)
Johann Wolfgang Goethe-University Frankfurt

27. Oct 2021 16:00h

Location: UKF, Building 23, auditorium 23-3

Hybrid Lecture

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»Multidisciplinary approaches in development of targeted protein degraders«
PROXIDRUGS Lecture Series
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Radoslaw Nowak
Dana-Farber Cancer Institute, Harvard Medical School

14. Sep 2021 17:00h

Location: Virtual Meeting

Virtual Lecture

»The Coming of Age of De Novo Protein Design«
TU Darmstadt Chemistry Seminar Series
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Prof. Dr. David Baker
Washington University, Seattle

22. Jun 2021 17:00h

Location: Virtual Meeting

Virtual Lecture


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»Mapping the Degradable Kinome Provides a Resource for Drug Discovery«
PROXIDRUGS Lecture Series
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Fleur M. Ferguson
University of California San Diego,
La Jolla,
US

01. Jun 2021 17:00h

Location: Virtual Lecture via Zoom

Virtual Lecture


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»Rapid response technologies for protein manufacturing and drug discovery«
TU Darmstadt Chemistry Seminar Series
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Prof. Dr. Bradley Pentelute
Massachusetts Institute of Technology Boston

25. May 2021 15:00h

Location: to be announced

Virtual Lecture

»Large-Scale Chemoproteomic Profiling Surveys the Degradable Proteome for Accelerated Degrader Development«
PROXIDRUGS Lecture Series
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Katherine A. Donovan
Dana-Farber Cancer Institute & Harvard Medical School,
Boston,
US

18. May 2021 16:00h

Location: Virtual Lecture via Zoom

Virtual Lecture


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»Regulation of Histone Methylation with Methyl-Lysine Reader Targeted Degraders«
PROXIDRUGS Lecture Series
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Lindsey Ingerman James
University of North Carolina,
Chapel Hill,
US

31. Mar 2021 16:00h

Location: Virtual Lecture via Zoom

Virtual Lecture


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»Lessons from thalidomide analogues as prototype molecular glue degraders«
PROXIDRUGS Lecture Series
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Philip Chamberlain
Neomorph, Inc.

16. Feb 2021 17:00h

Location: Virtual Lecture via Zoom

Virtual Lecture


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»Reimagining Druggability using Chemoproteomic Platforms«
PROXIDRUGS Lecture Series
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Daniel K. Nomura
University of California,
Berkeley,
US

16. Nov 2020 17:00h

Location: Virtual Lecture via Zoom

Virtual Lecture


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»Molecular Mechanisms of Small Molecule Mediated Ubiquitin Ligase Targeting«
PROXIDRUGS Lecture Series
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Eric Fischer
Dana-Farber Cancer Institute & Harvard Medical School,
Boston,
US

27. Oct 2020 16:30h

Location: Virtual Lecture via Zoom

Virtual Lecture


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»Probing Gene Control via Targeted Protein Degradation«
PROXIDRUGS Lecture Series
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Georg Winter
Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM),
Vienna,
AT

29. Sep 2020 16:00h

Location: Virtual Lecture via Zoom; Meeting-ID: 962 0881 2086 Kenncode: 612251

Virtual Lecture


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»Manipulating developmental pathways using proximity-inducing antibody modalities«
PROXIDRUGS Lecture Series
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Stephane Angers
Leslie Dan Faculty of Pharmacy,
University of Toronto,
CA

01. Sep 2020 16:00h

Location: Virtual Lecture via Zoom

Virtual Lecture


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»Multispecific drugs, induced proximity, and the future of biopharmaceutical innovation«
PROXIDRUGS Lecture Series
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Ray Deshaies
Senior Vice President,
Global Research,
AMGEN,
USA

25. Aug 2020 17:00h

Location: Virtual Lecture via Zoom

Virtual Lecture


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A BMBF Zukunftscluster Candidate
FKZ: 03ZK109AA