Anaplastic lymphoma kinase inhibitors

ALK signaling: Wild type (WT) ALK receptor (ALKr) requires ligand dimerization to trigger cellular signaling, conversely mutated ALKr and over expressed WT ALKr can efficiently signal even in presence of ligands. ALK fusions are ligand independent. ALK inhibitors (ALKi) block the ATP binding pocket (depicted as a blue oval). Mutation-driven resistant mechanisms can be overcome by second-generation compounds. A representation of the apo-crystal structure of ALK (shown in the low right side of the panel, (http://www.rcsb.org/pdb/explore/explore.do?structureId=3L9P).