Protein kinases have thus already been suggested as promising targets in drug design against schistosomiasis (74), selleck and their suitability as targets in cestodes has recently been demonstrated by Gelmedin et al. (75) who identified pyridinyl imidazoles, directed against the p38 subfamily of mitogen-activated protein kinases (MAPK), as a novel family of anti-Echinococcus compounds. A number of E. multilocularis protein kinases such as the Erk- and p38-like MAPKs EmMPK1 (76) and EmMPK2 (75), respectively, the MAPK kinases EmMKK1 and
EmMKK2 (77), or the Raf-like MAPK kinase kinase EmRaf (78) have already been characterized on the molecular and biochemical level, and particularly in the case of the two
MAPKs, functional biochemical ABT-888 in vivo assays have been established that can be used for compound screening (75,76). Of further interest are already characterized receptor kinases of the insulin- (EmIR; 79), the epidermal growth factor- (EmER; 80) and the transforming growth factor-β- (EmTR1; 81) receptor families that are expressed by the E. multilocularis metacestode stage and that are involved in host–parasite cross-communication by interacting with the evolutionary conserved cytokine- and hormone-ligands that are abundantly present in the intermediate host’s liver (1,72). In total, we could thus far identify ∼250 protein kinase-encoding genes on the genome assembly versions of E. multilocularis
(Table 3) and E. granulosus, the majority of which displays considerable homologies to orthologous genes in schistosomes, which could be particularly important for the design of compounds that have a broad spectrum of activity not only against cestodes but also against other parasitic flatworms. An important issue in rational drug design is not only the identification PFKL of targets that display structural and functional differences between the respective parasite and host components, thus ensuring that compounds with sufficient parasite specificity can be found, but also the general ‘druggability’ of the target, i.e., whether it contains structural features that favour interactions with small molecule compounds (82). Apart from protein kinases, several other protein families such as G-protein-coupled receptors (GPCR) or ligand-gated ion channels proved to be particularly druggable in previous compound screens and chemogenomic approaches (83). For a selection of protein families that are particularly suitable as drug targets, Table 3 lists the number of coding genes that we have identified using the current E. multilocularis genome assembly. In addition to a large number of protein kinases, several of which are already under study in the E.