%0 Journal Article %T Synthesis and biological evaluation of FJ-809, a compound originally described as MIM1 and inhibitor of the anti-apoptotic protein Mcl-1 %+ Institut des Sciences Chimiques de Rennes (ISCR) %+ Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE) %+ Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC) %+ Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN) %+ Université de Caen Normandie (UNICAEN) %+ Centre Régional de Mesures Physiques de l'Ouest (CRMPO) %+ Bioprojet-Biotech %A Justaud, Frédéric %A Paysant, Hippolyte %A Bastien Weiswald, Louis %A Jebahi, Abdelghani %A Jouanne, Marie %A Elie, Nicolas %A Voisin-Chiret, Anne, Sophie %A Roisnel, Thierry %A Orionne, Clément %A Levoin, Nicolas %A Poulain, Laurent %A Grée, René %< avec comité de lecture %@ 1144-0546 %J New Journal of Chemistry %I Royal Society of Chemistry %V 46 %N 19 %P 9119-9127 %8 2022 %D 2022 %R 10.1039/D1NJ05987D %K anti-apoptotic proteins %K Mcl-1 %K MIM1 %K thiazoles %K bioassays %K molecular modelling %K cancer %K anti-apoptotic proteins %Z Chemical Sciences/Medicinal ChemistryJournal articles %X The development of inhibitors of anti-apoptotic proteins, such as Mcl-1, is currently a very active area in the field of cancer research. One of the very first reported inhibitor of Mcl-1 was the molecule MIM1, but we have demonstrated recently that the structure of this compound had to be revised from 2 to the derivative 1 (FJ-809). In this paper we first develop a strategy to prepare unambiguously molecules such as 1 with a thiazol-3(2H)-yl)imino core, instead of the [2(3H)thiazolylidene]hydrazine previously found in MIM1 (2). Next a series of biological studies have been performed on 1, using IGROV1-R10 ovarian cancer cells as models, and they have been complemented by Fluorescence Polarisation Assays. These studies demonstrated that the new compound FJ-809 (1) was devoid of any significant activity on Mcl-1, contrary to 2. Then molecular modelling and molecular dynamic studies have been performed in order to elucidate the differences between FJ-809 and MIM1 in their interaction with the Mcl-1 protein. %G English %2 https://univ-rennes.hal.science/hal-03713884/document %2 https://univ-rennes.hal.science/hal-03713884/file/2022%20Publi%202%20MIM1%20NJC%20for%20Hal.pdf %L hal-03713884 %U https://univ-rennes.hal.science/hal-03713884 %~ INSERM %~ UNIV-RENNES1 %~ CNRS %~ INSA-RENNES %~ ENSC-RENNES %~ ISCR %~ SCR-CD %~ SCR_CPM %~ SCR-PNSCM %~ COMUE-NORMANDIE %~ UR1-SPM %~ ISCR-PRATS %~ INC-CNRS %~ UR1-UFR-SPM %~ UR1-HAL %~ ISCR-CORINT %~ UR1-SDLM %~ TEST-UR-CSS %~ UNIV-RENNES %~ UNICAEN %~ INSA-GROUPE %~ CERMN %~ ISCR-CORINT1 %~ UR1-MMS %~ ISCR-CORINT3 %~ INCIT %~ TEST2-HALCNRS %~ LABOS-XL-CHEM