Voltage-Gated Ion Channel-Targeted Library
Voltage-Gated Ion Channel-Targeted Library contains 5,000 compounds.
Voltage-gated ion channels were among the first ion channels to be identified. Voltage-gated ion channels contain sequence motifs that are necessary for their targeting, because these sequences may mediate interactions with proteins that are directly or indirectly involved with channel binding. Voltage-gated ion channels are formed by either one α-subunit that is a contiguous polypeptide that contains four repeats (domains I–IV) or four α-subunits, each with a single domain.  Sodium channels are closed and inactive at rest but undergo structural changes in response to membrane depolarization, leading to cycling of the channel through activated (open), inactive, and repriming states.
It is recognized that pain is a complex perception, which depends on electrical activity within sensory neurons. Within these neurons, voltage-gated sodium channels assist the generation and conduction of action potentials. This pivotal role of sodium channels in electrogenesis has made them attractive targets for pharmacotherapeutic approaches aimed at attenuating neuronal firing that result in pain. It was shown that even specific sodium channel isoforms are major contributors to chronic pain. Sodium channels can be modulated by a variety of small molecule pharmacological agents. Many of the clinically relevant modulators, such as lidocaine and carbamazepine, exhibit pronounced state-dependent binding where sodium channels that are rapidly and repeatedly activated and inactivated are easier blocked. 
 H. C. Lai and L. Y. Jan, “The distribution and targeting of neuronal voltage-gated ion channels,” Nat. Rev. Neurosci., vol. 7, no. 7, pp. 548–562, 2006, doi: 10.1038/nrn1938.
 S. D. Dib-Hajj, J. A. Black, and S. G. Waxman, “Voltage-gated sodium channels: Therapeutic targets for pain,” Pain Med., vol. 10, no. 7, pp. 1260–1269, 2009, doi: 10.1111/j.1526-4637.2009.00719.x.