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14-3-3STABS – Small molecule stabilizers of 14-3-3 Protein-Protein Interactions as novel drugs in cancer and neurodegenerative diseases

The objective of the application is the development and characterization of small molecule stabilizers of protein-protein interactions (Molecular Glues) as a novel class of biological tool compounds and potential therapeutic drugs for the treatment of cancer as well as Alzheimers and Parkinsons Disease, respectively. As biological targets we work on 14-3-3 proteins, an important class of adapter proteins that regulate a multitude of enzymes and proteins involved in the development of cancer and neurodegenerative diseases. 14-3-3 protein-protein interactions relevant in different cancers are Raf1 and YAP/TAZ. In Alzheimers and Parkinsons Disease the interaction of 14-3-3 proteins with AICD and -Synuclein are of potential therapeutic interest. The proposed project is based on the innovative approach to develop small molecules that bind selectively to the interaction surface of specific disease-related protein complexes thereby stabilizing their interaction which might lead to a beneficial therapeutic effect. This approach is complementary to todays strategy of developing inhibitors that target the active site of single enzymes and opens new possibilities to address undrugable targets. In fact, small molecule stabilizers of protein-protein-interactions have the potential to deliver a target-specific, target-oriented and more efficient modulation of the protein function than classical inhibitors. In this application, we propose two projects identifying and optimizing small molecules stabilizing 14-3-3 interactions with: 1. The cancer-relevant proteins Raf and YAP/TAZ 2. The Alzheimers and Parkinsons disease-relevant proteins AICD and -Synuclein. By stabilizing these protein-protein interactions the biological functions and biochemical properties like biochemical activity, subcellular localization and aggregation behaviour of the 14-3-3 target proteins are modulated.

  •  2012-01-01  2015-12-31
  • Overall Cost: 2.01 M.Eur
  •   > Lead Discovery Center
  • Other project partners
  • SE DE 
  • Industrial Manufacture 
  • FP7 Data provision: © European Union; Source: CORDIS, Cordis | This page is not provided by the European Commission 

 cancer   Development   protein   drug   enzymes   enzyme   drugs   cell   Bio   chemical   proteins   gene   treatment   molecular   disease   alzheimer   therapeutic   compounds   neurodegenerative   Small molecule   biological   innovative   Gen   diseases   molecule   parkinson   molecules   inhibitor   application   neuro   liver   compound   stabilizers   develop   lead   small molecules   Characterization   aggregation   biologic   strategy   biochemical   interaction   tool   degenerativ   cellular   protein complex   protein interaction   target   Complement   MPO   project   ABI   interactions   MIG   cancer   Development   protein   drug   enzymes   enzyme   drugs   cell   cancer   Development   protein   drug   enzymes   enzyme   drugs   cell   Bio   chemical   proteins   gene   treatment   molecular   disease   alzheimer   therapeutic   compounds   neurodegenerative   Small molecule   biological   innovative   Gen   diseases   molecule   parkinson   molecules   inhibitor   application   neuro   liver   compound   stabilizers   develop   lead   small molecules   Characterization   aggregation   biologic   strategy   biochemical   interaction   tool   degenerativ   cellular   protein complex   protein interaction   target   Complement   MPO   project   ABI   interactions   MIG 

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