| Doctorant : |
Alexandre DEMEYER
|
| Directeur de thèse : |
Fabrice FLEURY ,
Professeur Université |
| co-directeur de thèse : |
Pierre WEIGEL ,
Maître de conférences Université |
| Financement : |
PIRAMID |
| Date de la soutenance : |
vendredi 06 novembre 2020, 14h00 |
| Modalité : |
- Lieu : Amphithéâtre Pasteur, bâtiment 2, campus Lombarderie
|
| Jury : |
|
La réparation des dommages de l’ADN durant les thérapies anticancéreuses peuvent contribuer à la résistance des cellules tumorales, limitant ainsi l’efficacité du traitement. Chez l’homme, la réparation des cassures double-brin (CDB) de l’ADN par recombinaison homologue (RH) fait intervenir la protéine Rad51.
Cette protéine s’est révélée être impliquée dans les problèmes de résistance aux traitements anticancéreux puisque son inhibition par différentes approches a pour effet de sensibiliser les cellules cancéreuses aux traitements. Rad51 constitue donc une cible intéressante. Dans ce contexte la recherche d’inhibiteurs de Rad51 permet de proposer des solutions thérapeutiques afin d’améliorer les traitements anticancéreux actuels. Nous avons montré que des petites molécules étaient capables de moduler spécifiquement l’activité de Rad51 _in vitro_ et nos résultats cellulaires ont montré un effet chimiosensibilisateur.
Publications
2023
Demeyer, Alexandre; Fonteneau, Lucie; Liennard, Marion; Foyer, Claire; Weigel, Pierre; Laurent, Adèle; Lebreton, Jacques; Fleury, Fabrice; Mathé-Allainmat, Monique
Synthesis and Biological Evaluation of DIDS Analogues as Efficient Inhibitors of RAD51 Involved in Homologous Recombination Article de journal
Dans: Bioorg Med Chem Lett, p. 129261, 2023, ISSN: 1464-3405.
@article{pmid36990245,
title = {Synthesis and Biological Evaluation of DIDS Analogues as Efficient Inhibitors of RAD51 Involved in Homologous Recombination},
author = {Alexandre Demeyer and Lucie Fonteneau and Marion Liennard and Claire Foyer and Pierre Weigel and Adèle Laurent and Jacques Lebreton and Fabrice Fleury and Monique Mathé-Allainmat},
url = {hal-04234850v1 },
doi = {10.1016/j.bmcl.2023.129261},
issn = {1464-3405},
year = {2023},
date = {2023-03-01},
urldate = {2023-03-01},
journal = {Bioorg Med Chem Lett},
pages = {129261},
abstract = {RAD51 is a pivotal protein of the homologous recombination DNA repair pathway, and is overexpressed in some cancer cells, disrupting then the efficiency of cancer-treatments. The development of RAD51 inhibitors appears as a promising solution to restore these cancer cells sensitization to radio- or chemotherapy. From a small molecule identified as a modulator of RAD51, the 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), two series of analogues with small or bulky substituents on the aromatic parts of the stilbene moiety were prepared for a structure-activity relationship study. Three compounds, the cyano analogue (12), and benzamide (23) or phenylcarbamate (29) analogues of DIDS were characterized as novel potent RAD51 inhibitors with HR inhibition in the micromolar range.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
RAD51 is a pivotal protein of the homologous recombination DNA repair pathway, and is overexpressed in some cancer cells, disrupting then the efficiency of cancer-treatments. The development of RAD51 inhibitors appears as a promising solution to restore these cancer cells sensitization to radio- or chemotherapy. From a small molecule identified as a modulator of RAD51, the 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), two series of analogues with small or bulky substituents on the aromatic parts of the stilbene moiety were prepared for a structure-activity relationship study. Three compounds, the cyano analogue (12), and benzamide (23) or phenylcarbamate (29) analogues of DIDS were characterized as novel potent RAD51 inhibitors with HR inhibition in the micromolar range.
2020
Fleury, Fabrice; Demeyer, Alexandre; Weigel, Pierre; Chenais, Benoit; Mathé, Monique; Lebreton, Jacques
Disulfonate stilbenes for use in the treatment of proliferative diseases Patent
WO2020104634A1, 2020.
@patent{demeyer2020,
title = {Disulfonate stilbenes for use in the treatment of proliferative diseases},
author = {Fabrice Fleury and Alexandre Demeyer and Pierre Weigel and Benoit Chenais and Monique Mathé and Jacques Lebreton},
url = {https://worldwide.espacenet.com/patent/search/family/064564793/publication/WO2020104634A1?q=pn%3DWO2020104634A1},
year = {2020},
date = {2020-05-28},
number = {WO2020104634A1},
abstract = {This invention relates to compounds of general formula: wherein R0A and R0B are independently selected from hydrogen and pharmaceutically acceptable cations; and RA and RB are identical and selected from amide, carbamate, sulphonamide, azido, cyano and halide. The invention also relates to a pharmaceutical composition comprising a compound according to the invention. According to an embodiment, the composition further comprises another active ingredient, especially an antineoplastic agent. The invention also relates to a compound or a composition according to the invention for use as a medicament, especially a compound or a composition for use in the treatment of a proliferative disease such as for example cancer.},
keywords = {},
pubstate = {published},
tppubtype = {patent}
}
This invention relates to compounds of general formula: wherein R0A and R0B are independently selected from hydrogen and pharmaceutically acceptable cations; and RA and RB are identical and selected from amide, carbamate, sulphonamide, azido, cyano and halide. The invention also relates to a pharmaceutical composition comprising a compound according to the invention. According to an embodiment, the composition further comprises another active ingredient, especially an antineoplastic agent. The invention also relates to a compound or a composition according to the invention for use as a medicament, especially a compound or a composition for use in the treatment of a proliferative disease such as for example cancer.
Lien
