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EA 4258 | Centre d'études et de recherche sur le médicament de Normandie

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The treatment and prevention of most forms of cancer depend on more than one anti-apoptotic member. Thus, effective treatment may need to include the simultaneous inhibition of more than one anti-apoptotic protein of the Bcl-2 family. In this context, the discovery of dual inhibitors effective on Bcl-xL and Mcl-1 could play an important role in the treatment of cancer.
The methodology under consideration in the design of new potent dual inhibitors corresponds to a NMR analysis enabling to establish the initial affinities between the molecular fragments and the anti-apoptotic proteins. A library of fragments will thus be predefined by the molecular modelling tools (hot spots characterization and correspondence with these fragments) with a link to the alpha-mimetic structures developed in the laboratory. The biological evaluation of these potent dual inhibitors will be performed by our partners. Following initial results, renewed molecular modelling will enable us to optimize these dual inhibitors directed towards Bcl-xL and Mcl-1.
The programme receives funding from La Ligue Nationale contre le Cancer, the Regional Council of Normandy, the INC3M research federation (Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire) and the CRUNCh regional network  (Centre de Recherche Universitaire Normand de Chimie).

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Last update : July 4, 2016


Pr Anne-Sophie Voisin-Chiret
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