Traditional Chinese Herbs as Probes of P2X Receptors and other Ion Channels in the Pain Pathway

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Ion channels as drug targets. Ion channels are an important class of drug targets. About 13 % of all approved drugs target ligand-gated and voltage-gated ion channels (Overington, Al-Lazikani et al., 2006). Fostered by the widespread whole genome sequencing, an increasing number of mutations in ion channel genes are found to be linked with an increasing number of diseases. With this project, we want to screen TCMs commonly used again all forms of pain against as many ion channels of the pain pathway as possible. We will interpret the data both in regard of the ion channel structure and the chemical structure of the TCM ingredient to develop testable hypotheses (i) where exactly in the identified channel the TCMs ingredient binds and (ii) which molecular features are necessary for optimal molecular recognition of the ligand by the ion channel? We will use pharmacophore models to identify potential ligands in chemical databases by virtual screening and mutate ion channels on a structure-guided basis to verify predicted sites of action. Despite decades of research, there is an ongoing need for easily to handle, efficiently acting pain remedies that are well tolerated and neither lead to addiction nor cardiovascular or blood toxicity. This project has the potential to provide valuable insights in this respect.