virtual libraries; cell cycle; kinase inhibitor; x-ray crystallography; anti cancer drugs; structure based drug design
Kilchmann Falco, Marcaida Maria J, Kotak Sachin, Schick Thomas, Boss Silvan D, Awale Mahendra, Gönczy Pierre, Reymond Jean-Louis (2016), Discovery of a Selective Aurora A Kinase Inhibitor by Virtual Screening., in Journal of medicinal chemistry
, 59(15), 7188-211.
Roethlisberger P., Istrate A., Lopez M. J. Marcaida, Visini R., Stocker A., Reymond J. -L., Leumann C. J. (2016), X-ray structure of a lectin-bound DNA duplex containing an unnatural phenanthrenyl pair, in CHEMICAL COMMUNICATIONS
, 52(26), 4749-4752.
Bartoloni Marco, Jin Xian, Marcaida Maria Jose, Banha Joao, Dibonaventura Ivan, Bongoni Swathi, Bartho Kathrin, Graebner Olivia, Sefkow Michael, Darbre Tamis, Reymond Jean-Louis (2015), Bridged bicyclic peptides as potential drug scaffolds: synthesis, structure, protein binding and stability, in CHEMICAL SCIENCE
, 6(10), 5473-5490.
Christen Monika, Marcaida Maria J, Lamprakis Christos, Aeschimann Walter, Vaithilingam Jathana, Schneider Petra, Hilbert Manuel, Schneider Gisbert, Cascella Michele, Stocker Achim (2015), Structural insights on cholesterol endosynthesis: Binding of squalene and 2,3-oxidosqualene to supernatant protein factor., in Journal of structural biology
, 190(3), 261-70.
Yun J Marcaida MJ Eriksson KK Jamin H Fontana S Pichler WJ Yerly D. (2014), Oxypurinol directly and immediately activates the drug-specific T cells via the preferential use of HLA-B*58:01., in J Immunol
, 192(7), 2984-2993.
The aim of this project is to generate a new generation of Aurora A inhibitors for their use in functional studies and anti-cancer therapeutic applications. Our approach is original because ligands are searched within the set of yet unexplored molecules in the GDB database. This library contains all possible molecules (up to a certain size) that follow simple chemical constraints, most of them with no natural or synthetic origin. Innovative virtual screening methods using available Aurora A structural data will find hits. Crystal structures of Aurora A-ligand complexes will be pursued in order to understand the inhibition mechanism at the molecular level and optimise these compounds to avoid cross-reactivity. The potency and specificity of these inhibitors towards Aurora A will be tested using cellular and in vitro kinase assays. In light of the results obtained with this target, we will extend our approach towards inhibitors of other major disease-linked kinases.