Figure 5

Protein–protein interaction network of the proteins associated to fenbendazole-induced gene expression changes and its protein targets: each node represents a gene specified by the gene symbol, arrows indicate up- and downregulation of genes by fenbendazole (according to CMap data) and the rest of genes are in a rectangle. The genes that were up/down regulated in leukaemia disease signature are highlighted in red and blue, respectively. Predicted protein targets of fenbendazole are highlighted with green border. MYC, transcription factor that plays a role in cell cycle progression, apoptosis and cellular transformation, is a key gene in the topology of this network; it shows highest ‘betweenness’ in the connected part of the network. MYC is upregulated in the disease signature and in turn is downregulated by fenbendazole. On the other hand, RAF1, which is predicted as a target from the cheminformatics-side, is a first neighbour of many genes dysregulated in leukaemia, indicating the multi-faceted nature of the mode-of-action of a compound.