An overview of K+ channel pharmacology in general and a discussion of its medicinal chemistry which constitute targets for the treatment of neurological disorders, autoimmune diseases, and inflammation have been discussed. The discovery of K+ channel modulating drugs is increasingly assisted by structural information. Although currently, only KcsA and TBA are the only visualized example of a drug bound in the inner pore of a K+ channel, results of various mutational, electrophysiological, and ligand-binding experiments are increasingly interpreted in structural terms using homology modeling and ligand docking. It should be noted that the inner pore dimensions between the x ray structures of MthK, KvAP, and Kv1.2 vary widely. It is therefore advisable to interpret homology models of medicinally important K+ channels with caution. The huge diversity in the chemical structure of drugs modulating the same channel protein also poses as a challenge. Still, homology modeling and ligand docking are still popular methods in rationalizing huge and often controversial data on structure-activity relations of available ligands.
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