BRCA2-RAD51

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

Coordinatore	THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE    more  Organization address address: The Old Schools, Trinity Lane city: CAMBRIDGE postcode: CB2 1TN contact info Titolo: Ms. Nome: Renata Cognome: Schaeffer Email: send email Telefono: +44 1223 333543 Fax: +44 1223 332988
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	201˙049 €
EC contributo	201˙049 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2010-IIF
Funding Scheme	MC-IIF
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-03-01   -   2013-02-28

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE  Organization address address: The Old Schools, Trinity Lane city: CAMBRIDGE postcode: CB2 1TN contact info Titolo: Ms. Nome: Renata Cognome: Schaeffer Email: send email Telefono: +44 1223 333543 Fax: +44 1223 332988	UK (CAMBRIDGE)	coordinator	201˙049.60

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 Obiettivo del progetto (Objective)

'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.'