Research of new TTK kinase inhibitors by using structure-based pharmacophore modelling and docking experiments

Description

Multiple myeloma is a type of cancer for which, at the moment, no effective treatment is available. Computational studies on the identification of a pathway driving high-risk disease included the serine-threonine TTK kinase as one of the factors. [1] This enzyme is a crucial mitotic checkpoint during the centrosome duplication. Its inhibition leads to aneuploidy and ultimately to cell death. [2]Starting from the analysis of TTK-ligand complexes available on the Protein Data Bank, we implemented a virtual screening procedure that combines structure-based pharmacophore modelling, docking experiments, MM-GBSA and pose comparison. Subsequentially, the procedure includes a refinement of the virtual screening output with clustering and similarity search to ensure good diversity coverage. After final visual inspection, we proposed a list of potential new TTK inhibitors.[1] Furchtgott L, et al., blood 2017; 130:3029.[2] Pachis ST, Kops GJPL, Open Biol 2018; 8:180109.

Period	19 May 2019
Event title	XII EWDD - 12th European Workshop in Drug Design
Event type	Conference
Location	Siena, ItalyShow on map