The use of fragment-based drug discovery to develop novel small molecules that modulate the BRCA2-RAD51 interaction for the treatment of cancer

Projektinformationen

BRCA2-RAD51

ID Finanzhilfevereinbarung: 274569

Abgeschlossenes Projekt

Startdatum 1 März 2011

Enddatum 28 Februar 2013

Finanziert unter

• Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Gesamtkosten € 201 049,60

EU-Beitrag € 201 049,60

Koordiniert durch

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
United Kingdom

Ziel

"The proposed research is to develop a small molecule as drug candidate compound for the treatment of cancer. We will use fragment-based methods to disrupt the protein-protein interaction between the human recombinase RAD51, and the hub protein BRCA2. This interaction is essential for DNA repair by homologous DNA recombination (HDR), a key cellular pathway involved in the resistance of cancer cells to ionizing radiation and radio-mimetic drugs. The target site (i.e. Velcro pocket) is unique to RAD51 and binds the LFDE tetrapeptide motifs in BRCA2. A suite of biophysical techniques will be used to identify small chemical fragments that specifically bind to the Velcro pocket. Fragment hits will be developed by structure-guided synthesis into more potent inhibitors that disrupt RAD51-BRAC2 interaction impairing the HDR process. We foresee that these small molecule inhibitors will have broad applicability in combination with existing cancer treatments. Moreover it can be anticipated that a small molecules that target only the Velcro site of RAD51, thereby preventing interaction with BRAC2 protein without precluding RAD51 oligomerization, will be valuable chemical tools to uncover different mechanistic aspects of the HDR process in cells."

Wissenschaftliches Gebiet

• medical and health sciences › basic medicine › pharmacology and pharmacy › drug discovery
• natural sciences › biological sciences › biochemistry › biomolecules › proteins › proteomics
• natural sciences › biological sciences › genetics › DNA
• natural sciences › physical sciences › nuclear physics
• medical and health sciences › clinical medicine › oncology

Programm/Programme

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Thema/Themen

• FP7-PEOPLE-2010-IIF - Marie Curie Action: "International Incoming Fellowships"

Aufforderung zur Vorschlagseinreichung

FP7-PEOPLE-2010-IIF
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

MC-IIF - International Incoming Fellowships (IIF)

Koordinator

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

Kontakt Verwaltung

Renata Schaeffer (Ms.)

• EU-Beitrag: € 201 049,60
• Adresse: TRINITY LANE THE OLD SCHOOLS ; CB2 1TN Cambridge ; Vereinigtes Königreich
• Region: East of England › East Anglia › Cambridgeshire CC
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: Keine Daten