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Emergence

The designing of BH3-mimetic foldamers has been carried out with the financial support of the Normandy region’s ‘Emerging programmes’, the interregional collaborative fund Interreg IVA Innovative Synthesis: Culture and Entrepreneurship in CHEMistry and the European funding programme FEDER. Synthesis of a chemical library containing BH3-mimetic foldamers, characterization of foldamers by X-ray diffraction radiocrystallography and by NMR and of the hot spots by molecular modelling and NMR are carrying out (collaboration with Pr H Oulyadi, COBRA, CNRS UMR 6014, Rouen). The biological evaluation of these BH3-mimetic foldamers on ovarian cancer cell lines are being conducted at the BioTICLA unit (Dr L Poulain, INSERM UMR 1199, CLCC F Baclesse, Caen) and Pyridoclax turns out to have the greatest pro-apoptotic activity. The activity is directly linked to the inhibition of the Mcl-1 anti-apoptotic protein. All these results were included in the filing of a European patent, at present pending its international extension.  
Today the Canceropôle Nord Ouest is funding the in vivo preclinical trials to determine the validity of Pyridoclax and its hydrochloride, both in terms of the in situ evaluation of its effects on the proliferation and induction of the apoptosis and in terms of the in vivo evaluation of its anti-tumoral effect by using microPET imaging of brain glucose metabolism. At the same time, the specific binding site of Pyridoclax and its hydrochloride in the hydrophobic pocket of the Mcl-1 protein by NMR and molecular modelling is also being studied. The physicochemical and biopharmaceutical properties of Pyridoclax and its derivatives are being characterized by the Screening and Drugability Platform of CERMN. Galenic formulations notably based on the use of nano-emulsions are being developed in order to facilitate preclinical evaluation.
Today the North-West Region Cancer Research Technopole is funding the in vivo preclinical trials to determine the validity of Pyridoclax and its hydrochloride, both in terms of the in situ evaluation of its effects on the proliferation and induction of the apoptosis and in terms of the in vivo evaluation of its anti-tumoral effect by means of metabolic µTEP imagery. At the same time, the ‘hot spot’ specific link site of Pyridoclax and its hydrochloride in the hydrophobic pocket of the Mcl-1 protein by NMR and molecular modelization is also being studied. The physico-chemical and biopharmaceutical properties of Pyridoclax and its derivatives are being characterized by members of the Screening and Drugability Platform of CERMN. Dosage solutions notably based on the use of nano-emulsions are being developed in order to facilitate preclinical evaluation.

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Last update : July 4, 2016


CONTACT

Pr Anne-Sophie Voisin-Chiret
+33 (0)2 31 56 68 04
anne-sophie.voisin@unicaen.fr

Université de Caen Normandie
CERMN Centre détudes et de recherche sur le médicament de Normandie
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