Voltage-gated potassium channels as therapeutic targets

Voltage-gated K+ channels (KV) are involved in diverse physiological processes and offer important drug development opportunities for cancer and autoimmune diseases, as well as metabolic, neurological and cardiovascular disorders. Here, Wulff and colleagues discuss strategies to pharmacologically modulate KV channels and highlight recent progress in developing drugs that target specific KVsubfamilies. The human genome encodes 40 voltage-gated K+ channels (KV), which are involved in diverse physiological processes ranging from repolarization of neuronal and cardiac action potentials, to regulating Ca2+ signalling and cell volume, to driving cellular proliferation and migration. KV channels offer tremendous opportunities for the development of new drugs to treat cancer, autoimmune diseases and metabolic, neurological and cardiovascular disorders. This Review discusses pharmacological strategies for targeting KV channels with venom peptides, antibodies and small molecules, and highlights recent progress in the preclinical and clinical development of drugs targeting the KV1 subfamily, the KV7 subfamily (also known as KCNQ), KV10.1 (also known as EAG1 and KCNH1) and KV11.1 (also known as HERG and KCNH2) channels.