Sodium channel

Sodium

Neuroscience

Biology

Materials science

Venom

Extracellular

Receptor

Biochemistry

Purinergic receptor

Voltage-gated ion channel

Computational biology

Drug discovery

Immunology

Monoclonal antibody

Nanotechnology

Organic chemistry

Potassium channel

Modalities

Internal medicine

Sociology

Pharmacology

Medicine

Chemistry

Polyclonal antibodies

Biophysics

Antibody

Ion channel

Social science

Nature Reviews Drug Discovery

Ion channels play fundamental roles in both excitable and non-excitable tissues and therefore constitute attractive drug targets for myriad neurological, cardiovascular and metabolic diseases as well as for cancer and immunomodulation. However, achieving selectivity for specific ion channel subtypes with small-molecule drugs has been challenging, and there currently is a growing trend to target ion channels with biologics. One approach is to improve the pharmacokinetics of existing or novel venom-derived peptides. In parallel, after initial studies with polyclonal antibodies demonstrated the technical feasibility of inhibiting channel function with antibodies, multiple preclinical programmes are now using the full spectrum of available technologies to generate conventional monoclonal and engineered antibodies or nanobodies against extracellular loops of ion channels. After a summary of the current state of ion channel drug discovery, this Review discusses recent developments using the purinergic receptor channel P2X purinoceptor 7 (P2X7), the voltage-gated potassium channel KV1.3 and the voltage-gated sodium channel NaV1.7 as examples of targeting ion channels with biologics.

Antibodies and venom peptides: new modalities for ion channels