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Nat Rev Drug Discov. 2019 Feb 6. doi: 10.1038/s41573-019-0013-8. [Epub ahead of print]

Antibodies and venom peptides: new modalities for ion channels.

Author information

1
Department of Pharmacology, University of California Davis, Davis, CA, USA. hwulff@ucdavis.edu.
2
Saniona A/S, Ballerup, Denmark.
3
TetraGenetics Inc., Arlington, MA, USA.
4
Molecular Physiology Laboratory, Infection and Immunity Theme, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
5
Department of Physiology & Membrane Biology, University of California Davis, Davis, CA, USA.

Abstract

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.

PMID:
30728472
DOI:
10.1038/s41573-019-0013-8

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