Crystal Structures of Neurotrophin Receptors Kinase Domain.
Neurotrophins and their receptors (Trk) play key roles in the development of the nervous system and in cell survival. Trk receptors are therefore attractive pharmacological targets for brain disorders as well as for cancers. While the druggability of the extracellular domain of the receptors, that specifically binds neurotrophins, is yet to be proven, the intracellular kinase domains are attractive targets for small-molecule binding. The recent crystal structures of the three isoforms of the Trk family, TrkA, TrkB, and TrkC have been described in their apo forms and in complex with potent and selective pan-Trk inhibitors. The description of the kinase domain of each of the isoforms will be discussed in their apo forms or bound to potent inhibitors of interest in cancer therapy. Nononcology indications and selectivity issues will also be discussed.
['Bertrand|T|T|']
D000255:Adenosine Triphosphate D000818:Animals D000970:Antineoplastic Agents D001051:Apoenzymes D001665:Binding Sites D020134:Catalytic Domain D006801:Humans D007527:Isoenzymes D008024:Ligands D008562:Membrane Glycoproteins D008958:Models, Molecular D008968:Molecular Conformation D009414:Nerve Growth Factors D010649:Phenylalanine D011487:Protein Conformation D054730:Protein Interaction Domains and Motifs D047428:Protein Kinase Inhibitors D020917:Receptor, trkA D020813:Receptor, trkB D020812:Receptor, trkC D040681:Structural Homology, Protein
Structure Kinase Pharmacology Selectivity Inhibitors Drug design