Voltage sensor interaction site for selective small molecule inhibitors of voltage-gated sodium channels

A quantitative description of membrane current and its application to conduction and excitation in nerve

Hodgkin, A. L., & Huxley, A. F. (1952) · The Journal of Physiology · doi:10.1113/jphysiol.1952.sp004764 · Cited by 23,191 · see citing works

An SCN9A channelopathy causes congenital inability to experience pain

Cox, J. J., Reimann, F. M., Nicholas, A. K., Thornton, G., Roberts, E., Springell, K., Karbani, G., Jafri, H., Mannan, J., Raashid, Y., et al. (2006) · Nature · doi:10.1038/nature05413 · Cited by 1,605 · see citing works

The crystal structure of a voltage-gated sodium channel

Payandeh, J., Scheuer, T., Zheng, N., & Catterall, W. A. (2011) · Nature · doi:10.1038/nature10238 · Cited by 1,431 · see citing works

Molecular Determinants of State-Dependent Block of Na + Channels by Local Anesthetics

Ragsdale, D. S., McPhee, J. C., Scheuer, T., & Catterall, W. A. (1994) · Science · doi:10.1126/science.8085162 · Cited by 839 · see citing works

Voltage‐gated sodium channels at 60: structure, function and pathophysiology

Catterall, W. A. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2011.224204 · Cited by 728 · see citing works

Voltage-gated ion channels and gating modifier toxins

Catterall, W. A., Cestèle, S., Yarov-Yarovoy, V. M., Yu, F. H., Konoki, K., & Scheuer, T. (2006) · Toxicon · doi:10.1016/j.toxicon.2006.09.022 · Cited by 641 · see citing works

Ion Channel Voltage Sensors: Structure, Function, and Pathophysiology

Catterall, W. A. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.021 · Cited by 570 · see citing works

Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels.

Ragsdale, D. S., McPhee, J. C., Scheuer, T., & Catterall, W. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.17.9270 · Cited by 500 · see citing works

Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders

Mantegazza, M., Curia, G., Biagini, G., Ragsdale, D. S., & Avoli, M. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70059-4 · Cited by 457 · see citing works

Molecular Determinants of High Affinity Binding of α-Scorpion Toxin and Sea Anemone Toxin in the S3-S4 Extracellular Loop in Domain IV of the Na+ Channel α Subunit

Rogers, J. C., Qu, Y., Tanada, T. N., Scheuer, T., & Catterall, W. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.27.15950 · Cited by 411 · see citing works

Upregulation of Sodium Channel Nav1.3 and Functional Involvement in Neuronal Hyperexcitability Associated with Central Neuropathic Pain after Spinal Cord Injury

Hains, B. C., Klein, J. P., Saab, C. Y., Craner, M. J., Black, J. A., & Waxman, S. G. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-26-08881.2003 · Cited by 384 · see citing works

Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders

Drenth, J. P. H., & Waxman, S. G. (2007) · Journal of Clinical Investigation · doi:10.1172/jci33297 · Cited by 373 · see citing works

Structure and function of voltage‐gated sodium channels

Marbán, E., Yamagishi, T., & Tomaselli, G. F. (1998) · The Journal of Physiology · doi:10.1111/j.1469-7793.1998.647bp.x · Cited by 362 · see citing works

A single point mutation confers tetrodotoxin and saxitoxin insensitivity on the sodium channel II

Noda, M., Suzuki, H., Numa, S., & Stühmer, W. (1989) · FEBS Letters · doi:10.1016/0014-5793(89)81531-5 · Cited by 342 · see citing works

ProTx-II, a Selective Inhibitor of NaV1.7 Sodium Channels, Blocks Action Potential Propagation in Nociceptors

Schmalhofer, W. A., Calhoun, J. D., Burrows, R., Bailey, T., Köhler, M. G., Weinglass, A. B., Kaczorowski, G. J., García, M. L., Koltzenburg, M., & Priest, B. T. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.047670 · Cited by 301 · see citing works

Deconstructing voltage sensor function and pharmacology in sodium channels

Bosmans, F., Martin‐Eauclaire, M., & Swartz, K. J. (2008) · Nature · doi:10.1038/nature07473 · Cited by 261 · see citing works

Frequency and Voltage-Dependent Inhibition of Type IIA Na+ Channels, Expressed in a Mammalian Cell Line, by Local Anesthetic, Antiarrhythmic, and Anticonvulsant Drugs

Ragsdale, D. S., Scheuer, T., & Catterall, W. A. (1991) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)15395-9 · Cited by 226 · see citing works

Voltage-Gated Sodium Channels: Therapeutic Targets for Pain

Dib‐Hajj, S. D., Black, J. A., & Waxman, S. G. (2009) · Pain Medicine · doi:10.1111/j.1526-4637.2009.00719.x · Cited by 201 · see citing works

Local anesthetic systemic toxicity

Wolfe, J. W., & Butterworth, J. F. I. (2011) · Current Opinion in Anaesthesiology · doi:10.1097/aco.0b013e32834a9394 · Cited by 157 · see citing works

Voltage-gated sodium channels in pain states: Role in pathophysiology and targets for treatment

Dib‐Hajj, S. D., Binshtok, A. M., Cummins, T., Jarvis, M. F., Samad, T. A., & Zimmermann, K. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.12.005 · Cited by 151 · see citing works

Targeting voltage sensors in sodium channels with spider toxins

Bosmans, F., & Swartz, K. J. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.12.007 · Cited by 141 · see citing works

The Tarantula Toxins ProTx-II and Huwentoxin-IV Differentially Interact with Human Nav1.7 Voltage Sensors to Inhibit Channel Activation and Inactivation

Xiao, Y., Blumenthal, K. M., Jackson, J. O., Liang, S., & Cummins, T. (2010) · Molecular Pharmacology · doi:10.1124/mol.110.066332 · Cited by 139 · see citing works

Mapping the receptor site for α-scorpion toxins on a Na + channel voltage sensor

Wang, J., Yarov-Yarovoy, V. M., Kahn, R., Gordon, D., Gurevitz, M., Scheuer, T., & Catterall, W. A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112320108 · Cited by 130 · see citing works

The Tetrodotoxin Binding Site Is within the Outer Vestibule of the Sodium Channel

Fozzard, H. A., & Lipkind, G. M. (2010) · Marine Drugs · doi:10.3390/md8020219 · Cited by 127 · see citing works

The Sodium Channel as a Target for Local Anesthetic Drugs

Fozzard, H. A., Sheets, M. F., & Hanck, D. A. (2011) · Frontiers in Pharmacology · doi:10.3389/fphar.2011.00068 · Cited by 125 · see citing works

State-dependent block of voltage-gated Na+ channels by amitriptyline via the local anesthetic receptor and its implication for neuropathic pain

Wang, G. K., Russell, C., & Wang, S. (2004) · Pain · doi:10.1016/j.pain.2004.03.018 · Cited by 121 · see citing works

Subtype‐selective targeting of voltage‐gated sodium channels

England, S., & de Groot, M. J. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00437.x · Cited by 115 · see citing works

Sodium channel expression and the molecular pathophysiology of pain after SCI

Hains, B. C., & Waxman, S. G. (2007) · Progress in brain research · doi:10.1016/s0079-6123(06)61013-3 · Cited by 107 · see citing works

Differential interactions of lamotrigine and related drugs with transmembrane segment IVS6 of voltage-gated sodium channels

Liu, G., Yarov-Yarovoy, V. M., Nobbs, M. S., Clare, J. J., Scheuer, T., & Catterall, W. A. (2003) · Neuropharmacology · doi:10.1016/s0028-3908(02)00400-8 · Cited by 99 · see citing works

Inhibition of Sodium Channel Gating by Trapping the Domain II Voltage Sensor with Protoxin II

Sokolov, S., Kraus, R. L., Scheuer, T., & Catterall, W. A. (2007) · Molecular Pharmacology · doi:10.1124/mol.107.041046 · Cited by 95 · see citing works

Local Anesthetics

Yanagidate, F., & Strichartz, G. R. (2007) · Springer eBooks · doi:10.1007/978-3-540-33823-9_4 · Cited by 90 · see citing works

Abnormal Ventricular Repolarization Mimicking Myocardial Infarction After Heterocyclic Antidepressant Overdose

Bolognesi, R., Tsialtas, D., Vasini, P., Conti, M., & Manca, C. (1997) · The American Journal of Cardiology · doi:10.1016/s0002-9149(96)00727-8 · Cited by 79 · see citing works

Mapping of scorpion toxin receptor sites at voltage-gated sodium channels

Gurevitz, M. (2012) · Toxicon · doi:10.1016/j.toxicon.2012.03.022 · Cited by 77 · see citing works

Animal Peptides Targeting Voltage-Activated Sodium Channels

Billen, B., Bosmans, F., & Tytgat, J. (2008) · Current Pharmaceutical Design · doi:10.2174/138161208785777423 · Cited by 75 · see citing works

Combinatorial Interaction of Scorpion Toxins Lqh-2, Lqh-3, and LqhαIT with Sodium Channel Receptor Sites-3

Leipold, E., Lu, S., Gordon, D., Hansel, A., & Heinemann, S. H. (2004) · Molecular Pharmacology · doi:10.1124/mol.65.3.685 · Cited by 69 · see citing works

Blockers of Voltage-Gated Sodium Channels for the Treatment of Central Nervous System Diseases

Tarnawa, I., Bölcskei, H., & Kocsis, P. (2007) · Recent Patents on CNS Drug Discovery · doi:10.2174/157488907779561754 · Cited by 69 · see citing works

Targeting voltage-gated sodium channels for pain therapy

Clare, J. J. (2009) · Expert Opinion on Investigational Drugs · doi:10.1517/13543780903435340 · Cited by 66 · see citing works

Conotoxins Targeting Neuronal Voltage-Gated Sodium Channel Subtypes: Potential Analgesics?

Knapp, O., McArthur, J. R., & Adams, D. J. (2012) · Toxins · doi:10.3390/toxins4111236 · Cited by 61 · see citing works

Voltage-Gated Sodium Channel Blockers; Target Validation and Therapeutic Potential

Wood, J. N., & Boorman, J. P. (2005) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026054367584 · Cited by 59 · see citing works

Sodium channels and nociception: recent concepts and therapeutic opportunities

Krafte, D. S., & Bannon, A. W. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2007.09.007 · Cited by 55 · see citing works

Functional properties and toxin pharmacology of a dorsal root ganglion sodium channel viewed through its voltage sensors

Bosmans, F., Puopolo, M., Martin‐Eauclaire, M., Bean, B. P., & Swartz, K. J. (2011) · The Journal of General Physiology · doi:10.1085/jgp.201110614 · Cited by 54 · see citing works

The action potential: From voltage-gated conductances to molecular structures

Bezanilla, F. (2006) · Biological Research · doi:10.4067/s0716-97602006000300005 · Cited by 34 · see citing works

Sodium Channel Inhibiting Marine Toxins

Llewellyn, L. E. (2009) · Progress in molecular and subcellular biology · doi:10.1007/978-3-540-87895-7_3 · Cited by 31 · see citing works

A Point Mutation at F1737 of the Human Na v 1.7 Sodium Channel Decreases Inhibition by Local Anesthetics

Panigel, J., & Cook, S. P. (2011) · Journal of Neurogenetics · doi:10.3109/01677063.2011.629702 · Cited by 24 · see citing works

Isoform-Selective Voltage-Gated Na + Channel Modulators as Next-Generation Analgesics

England, S., & Rawson, D. J. (2010) · Future Medicinal Chemistry · doi:10.4155/fmc.10.26 · Cited by 21 · see citing works

New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain

Feldman, E. L., Nave, K.-A., Jensen, T. S., & Bennett, D. L. H. (2017) · Neuron · doi:10.1016/j.neuron.2017.02.005 · Cited by 915 · see citing works

The Role of Voltage-Gated Sodium Channels in Pain Signaling

Bennett, D. L., Clark, A. J., Huang, J., Waxman, S. G., & Dib-Hajj, S. D. (2019) · Physiological Reviews · doi:10.1152/physrev.00052.2017 · Cited by 730 · see citing works

Voltage-gated sodium channels: structure, function, pharmacology, and clinical indications

de Lera Ruiz, M., & Kraus, R. L. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm501981g · Cited by 548 · see citing works

Breaking barriers to novel analgesic drug development

Yekkirala, A. S., Roberson, D. P., Bean, B. P., & Woolf, C. J. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.87 · Cited by 366 · see citing works

Progress in Understanding and Treating SCN2A-Mediated Disorders

Sanders, S. J., Campbell, A. J., Cottrell, J. R., Moller, R. S., Wagner, F. F., Auldridge, A. L., Bernier, R. A., Catterall, W. A., Chung, W. K., Empfield, J. R., et al. (2018) · Trends in Neurosciences · doi:10.1016/j.tins.2018.03.011 · Cited by 338 · see citing works

The hitchhiker’s guide to the voltage-gated sodium channel galaxy

Ahern, C. A., Payandeh, J., Bosmans, F., & Chanda, B. (2015) · The Journal of General Physiology · doi:10.1085/jgp.201511492 · Cited by 358 · see citing works

Structural basis of Nav1.7 inhibition by an isoform-selective small-molecule antagonist

Ahuja, S., Mukund, S., Deng, L., Khakh, K., Chang, E., Ho, H., Shriver, S., Young, C., Lin, S., Johnson, J. P., et al. (2015) · Science · doi:10.1126/science.aac5464 · Cited by 319 · see citing works

Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain

Osteen, J. D., Herzig, V., Gilchrist, J. M., Emrick, J. J., Zhang, C., Wang, X., Castro, J., Garcia‐Caraballo, S., Grundy, L., Rychkov, G. Y., et al. (2016) · Nature · doi:10.1038/nature17976 · Cited by 286 · see citing works

Peptide therapeutics from venom: Current status and potential

Pennington, M. W., Czerwiński, A. A., & Norton, R. S. (2017) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2017.09.029 · Cited by 278 · see citing works

An artificial intelligence accelerated virtual screening platform for drug discovery

(2024) · doi:10.1038/s41467-024-52061-7 · Cited by 259 · see citing works

NaV1.9: a sodium channel linked to human pain

Dib‐Hajj, S. D., Black, J. A., & Waxman, S. G. (2015) · Nature reviews. Neuroscience · doi:10.1038/nrn3977 · Cited by 210 · see citing works

The Role of the Dorsal Root Ganglion in the Development of Neuropathic Pain

Krames, E. S. (2014) · Pain Medicine · doi:10.1111/pme.12413 · Cited by 209 · see citing works

Structural Basis for Pharmacology of Voltage-Gated Sodium and Calcium Channels

Catterall, W. A., & Swanson, T. M. (2015) · Molecular Pharmacology · doi:10.1124/mol.114.097659 · Cited by 192 · see citing works

Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release

Alexandrou, A. J., Brown, A. R., Chapman, M. L., Estación, M., Turner, J., Mis, M. A., Wilbrey, A. L., Payne, E. C., Gutteridge, A., Cox, P. J., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0152405 · Cited by 190 · see citing works

Distribution and function of voltage-gated sodium channels in the nervous system

Wang, J., Ou, S., & Wang, Y. (2017) · Channels · doi:10.1080/19336950.2017.1380758 · Cited by 190 · see citing works

Recent progress in sodium channel modulators for pain

Bagal, S. K., Chapman, M. L., Marron, B. E., Prime, R., Storer, R. I., & Swain, N. A. (2014) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2014.06.038 · Cited by 181 · see citing works

Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery

Imbrici, P., Liantonio, A., Camerino, G. M., Bellis, M. D., Camerino, C., Mele, A., Giustino, A., Pierno, S., Luca, A. D., Tricarico, D., et al. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00121 · Cited by 151 · see citing works

Voltage gated sodium channels as drug discovery targets

Bagal, S. K., Marron, B. E., Owen, R. M., Storer, R. I., & Swain, N. A. (2015) · Channels · doi:10.1080/19336950.2015.1079674 · Cited by 147 · see citing works

Sodium Channels in Human Pain Disorders: Genetics and Pharmacogenomics

Dib‐Hajj, S. D., & Waxman, S. G. (2019) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070918-050144 · Cited by 144 · see citing works

Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a

Deuis, J. R., Dekan, Z., Wingerd, J. S., Smith, J. J. L., Munasinghe, N. R., Bhola, R. F., Imlach, W. L., Herzig, V., Armstrong, D. A., Rosengren, K. J., et al. (2017) · Scientific Reports · doi:10.1038/srep40883 · Cited by 137 · see citing works

NaV1.7 as a pain target – From gene to pharmacology

Vetter, I., Deuis, J. R., Mueller, A., Israel, M. R., Starobova, H., Zhang, A. H., Rash, L. D., & Mobli, M. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.11.015 · Cited by 127 · see citing works

Aberrant epilepsy-associated mutant Nav1.6 sodium channel activity can be targeted with cannabidiol

Patel, R. R., Barbosa, C., Brustovetsky, T., Brustovetsky, N., & Cummins, T. (2016) · Brain · doi:10.1093/brain/aww129 · Cited by 122 · see citing works

Insensitivity to pain induced by a potent selective closed-state Nav1.7 inhibitor

Flinspach, M. L., Xu, Q., Piekarz, A. D., Fellows, R., Hagan, R., Gibbs, A., Liu, Y., Neff, R. A., Freedman, J., Eckert, W. A., et al. (2017) · Scientific Reports · doi:10.1038/srep39662 · Cited by 119 · see citing works

Analgesic Effects of GpTx-1, PF-04856264 and CNV1014802 in a Mouse Model of NaV1.7-Mediated Pain

Deuis, J. R., Wingerd, J. S., Winter, Z., Durek, T., Dekan, Z., de Sousa, S. R., Zimmermann, K., Hoffmann, T., Weidner, C., Nassar, M. A., et al. (2016) · Toxins · doi:10.3390/toxins8030078 · Cited by 117 · see citing works

Fifteen years of NaV1.7 channels as an analgesic target: Why has excellent in vitro pharmacology not translated into in vivo analgesic efficacy?

Eagles, D. A., Chow, C. Y., & King, G. F. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15327 · Cited by 117 · see citing works

Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis

Fu, W., Vasylyev, D. V., Bi, Y., Zhang, M., Sun, G., Khleborodova, A., Huang, G., Zhao, L., Zhou, R., Li, Y., et al. (2024) · Nature · doi:10.1038/s41586-023-06888-7 · Cited by 115 · see citing works

Challenges and Opportunities for Therapeutics Targeting the Voltage-Gated Sodium Channel Isoform Na V 1.7

Mulcahy, J. V., Pajouhesh, H., Beckley, J. T., Delwig, A., Bois, J. D., & Hunter, J. C. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01906 · Cited by 101 · see citing works

Sodium channels in pain disorders: pathophysiology and prospects for treatment

Dib‐Hajj, S. D., Geha, P., & Waxman, S. G. (2017) · Pain · doi:10.1097/j.pain.0000000000000854 · Cited by 99 · see citing works

<scp><i>SCN3A</i></scp>‐Related Neurodevelopmental Disorder: A Spectrum of Epilepsy and Brain Malformation

Zaman, T., Helbig, K. L., Clatot, J., Thompson, C. H., Kang, S. K., Stouffs, K., Jansen, A. E., Verstraete, L., Jacquinet, A., Parrini, E., et al. (2020) · Annals of Neurology · doi:10.1002/ana.25809 · Cited by 94 · see citing works

Discovery of Clinical Candidate 4-[2-(5-Amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-1,3-thiazol-4-ylbenzenesulfonamide (PF-05089771): Design and Optimization of Diaryl Ether Aryl Sulfonamides as Selective Inhibitors of NaV1.7

Swain, N. A., Batchelor, D. V., Beaudoin, S., Bechle, B. M., Bradley, P. A., Brown, A. D., Brown, B., Butcher, K. J., Butt, R. P., Chapman, M. L., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00598 · Cited by 89 · see citing works

Structural mapping of Nav1.7 antagonists

Wu, Q., Huang, J., Fan, X., Wang, K., Jin, X., Huang, G., Li, J., Pan, X., & Yan, N. (2023) · Nature Communications · doi:10.1038/s41467-023-38942-3 · Cited by 85 · see citing works

MiR-30b Attenuates Neuropathic Pain by Regulating Voltage-Gated Sodium Channel Nav1.3 in Rats

Su, S., Shao, J., Zhao, Q., Ren, X., Cai, W., Li, L., Bai, Q., Chen, X., Xu, B., Wang, J., et al. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00126 · Cited by 84 · see citing works

NBI-921352, a first-in-class, NaV1.6 selective, sodium channel inhibitor that prevents seizures in Scn8a gain-of-function mice, and wild-type mice and rats

Johnson, J., Focken, T., Khakh, K., Tari, P. K., Dube, C., Williams, A., Andrez, J.-C., Bankar, G., Bogucki, D., Burford, K., et al. (2022) · eLife · doi:10.7554/elife.72468 · Cited by 80 · see citing works

Bacterial Voltage-Gated Sodium Channels (BacNaVs) from the Soil, Sea, and Salt Lakes Enlighten Molecular Mechanisms of Electrical Signaling and Pharmacology in the Brain and Heart

Payandeh, J., & Minor, D. L. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2014.08.010 · Cited by 79 · see citing works

Structural Pharmacology of Voltage-Gated Sodium Channels

Noreng, S., Li, T., & Payandeh, J. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.166967 · Cited by 78 · see citing works

Selective NaV1.7 Antagonists with Long Residence Time Show Improved Efficacy against Inflammatory and Neuropathic Pain

Bankar, G. R., Goodchild, S. J., Howard, S., Nelkenbrecher, K., Waldbrook, M., Dourado, M., Shuart, N. G., Lin, S., Young, C., Xie, Z., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.08.063 · Cited by 78 · see citing works

Discovery of Aryl Sulfonamides as Isoform-Selective Inhibitors of NaV1.7 with Efficacy in Rodent Pain Models

Focken, T., Liu, S., Chahal, N., Dauphinais, M., Grimwood, M., Chowdhury, S., Hemeon, I., Bichler, P., Bogucki, D. E., Waldbrook, M., et al. (2016) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.5b00447 · Cited by 73 · see citing works

Na+channel function, regulation, structure, trafficking and sequestration

Chen‐Izu, Y., Shaw, R. M., Pitt, G. S., Yarov-Yarovoy, V. M., Sack, J. T., Abriel, H., Aldrich, R. W., Belardinelli, L., Cannell, M. B., Catterall, W. A., et al. (2015) · The Journal of Physiology · doi:10.1113/jphysiol.2014.281428 · Cited by 72 · see citing works

Sodium Channels and Pain

Habib, A. M., Wood, J. N., & Cox, J. J. (2015) · Handbook of experimental pharmacology · doi:10.1007/978-3-662-46450-2_3 · Cited by 71 · see citing works

Na V 1.7 as a Pharmacogenomic Target for Pain: Moving Toward Precision Medicine

Yang, Y., Mis, M. A., Estación, M., Dib‐Hajj, S. D., & Waxman, S. G. (2018) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.11.010 · Cited by 71 · see citing works

Structural basis for modulation of human NaV1.3 by clinical drug and selective antagonist

Li, X., Xu, F., Xu, H., Zhang, S., Gao, Y., Zhang, H., Dong, Y., Zheng, Y., Yang, B., Sun, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28808-5 · Cited by 71 · see citing works

Voltage-gated sodium channels in excitable cells as drug targets

Alsaloum, M., Dib‐Hajj, S. D., Page, D. A., Ruben, P. C., Krainer, A. R., & Waxman, S. G. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01108-x · Cited by 66 · see citing works

Neuropathic pain: preclinical and early clinical progress with voltage-gated sodium channel blockers

Kushnarev, M., Pirvulescu, I., Candido, K. D., & Knežević, N. N. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1728254 · Cited by 69 · see citing works

Optical electrophysiology for probing function and pharmacology of voltage-gated ion channels

Zhang, H., Reichert, E. C., & Cohen, A. E. (2016) · eLife · doi:10.7554/elife.15202 · Cited by 62 · see citing works

Inhibition of the Ubc9 E2 SUMO-conjugating enzyme–CRMP2 interaction decreases NaV1.7 currents and reverses experimental neuropathic pain

François‐Moutal, L., Dustrude, E. T., Wang, Y., Brustovetsky, T., Dorame, A., Ju, W., Moutal, A., Perez‐Miller, S., Brustovetsky, N., Gokhale, V. M., et al. (2018) · Pain · doi:10.1097/j.pain.0000000000001294 · Cited by 57 · see citing works

Pharmacologic Characterization of AMG8379, a Potent and Selective Small Molecule Sulfonamide Antagonist of the Voltage-Gated Sodium Channel NaV1.7

Kornecook, T. J., Yin, R., Altmann, S. M., Be, X., Berry, V. M., Ilch, C. P., Jarosh, M., Johnson, D., Lee, J. H., Lehto, S. G., et al. (2017) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.239590 · Cited by 54 · see citing works

Antiallodynic effects of the selective NaV1.7 inhibitor Pn3a in a mouse model of acute postsurgical pain: evidence for analgesic synergy with opioids and baclofen

Mueller, A., Starobova, H., Morgan, M., Dekan, Z., Cheneval, O., Schroeder, C. I., Alewood, P. F., Deuis, J. R., & Vetter, I. (2019) · Pain · doi:10.1097/j.pain.0000000000001567 · Cited by 54 · see citing works

Druggability of Voltage-Gated Sodium Channels—Exploring Old and New Drug Receptor Sites

Wisedchaisri, G., & El-Din, T. M. G. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.858348 · Cited by 53 · see citing works

Biophysical and Pharmacological Characterization of Nav1.9 Voltage Dependent Sodium Channels Stably Expressed in HEK-293 Cells

Lin, Z., Santos, S., Padilla, K. M., Printzenhoff, D., & Castle, N. A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0161450 · Cited by 53 · see citing works

Treatment of chronic pain by designer cells controlled by spearmint aromatherapy

Wang, H., Xie, M., Hamri, G. C., Ye, H., & Fussenegger, M. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0192-3 · Cited by 53 · see citing works

Differential effect of lacosamide on Nav1.7 variants from responsive and non-responsive patients with small fibre neuropathy

Labau, J. I. R., Estación, M., Tanaka, B. S., de Greef, B. T. A., Hoeijmakers, J. G. J., Geerts, M., Gerrits, M. M., Smeets, H. J. M., Faber, C. G., Merkies, I. S. J., et al. (2020) · Brain · doi:10.1093/brain/awaa016 · Cited by 53 · see citing works

The Selective Nav1.7 Inhibitor, PF-05089771, Interacts Equivalently with Fast and Slow Inactivated Nav1.7 Channels

Theile, J. W., Fuller, M. D., & Chapman, M. L. (2016) · Molecular Pharmacology · doi:10.1124/mol.116.105437 · Cited by 52 · see citing works

Sulfonamides as Selective NaV1.7 Inhibitors: Optimizing Potency and Pharmacokinetics While Mitigating Metabolic Liabilities

Weiss, M. M., Dineen, T. A., Marx, I. E., Altmann, S., Boezio, A. A., Bregman, H. S., Chu‐Moyer, M. Y., DiMauro, E. F., Bojić, E. F., Foti, R., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01851 · Cited by 52 · see citing works

Structural Advances in Voltage-Gated Sodium Channels

Jiang, D., Zhang, J., & Xia, Z. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.908867 · Cited by 51 · see citing works

Sodium channel NaV1.3 is important for enterochromaffin cell excitability and serotonin release

Strege, P., Knutson, K. R., Eggers, S. J., Li, J. H., Wang, F., Linden, D., Szurszewski, J., Milescu, L., Leiter, A., Farrugia, G., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-15834-3 · Cited by 45 · see citing works

Studies Examining the Relationship between the Chemical Structure of Protoxin II and Its Activity on Voltage Gated Sodium Channels

Park, J. H., Carlin, K. P., Wu, G., Ilyin, V. I., Musza, L. L., Blake, P. R., & Kyle, D. J. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500687u · Cited by 48 · see citing works

Discovery of selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors with pain efficacy in mice

Roecker, A. J., Egbertson, M. S., Jones, K. L., Gomez, R. P., Kraus, R. L., Li, Y., Koser, A. J., Urban, M. O., Klein, R. M., Clements, M. K., et al. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.03.085 · Cited by 48 · see citing works

Protonation state of inhibitors determines interaction sites within voltage-gated sodium channels

Buyan, A., Sun, D., & Corry, B. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1714131115 · Cited by 48 · see citing works

The structure, dynamics and selectivity profile of a NaV1.7 potency-optimised huwentoxin-IV variant

Rahnama, S., Deuis, J. R., Cardoso, F. C., Ramanujam, V., Lewis, R. J., Rash, L. D., King, G. F., Vetter, I., & Mobli, M. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173551 · Cited by 46 · see citing works

Structure and Function of μ-Conotoxins, Peptide-Based Sodium Channel Blockers with Analgesic Activity

Green, B. R., Bulaj, G. W., & Norton, R. S. (2014) · Future Medicinal Chemistry · doi:10.4155/fmc.14.107 · Cited by 45 · see citing works

Application of a Parallel Synthetic Strategy in the Discovery of Biaryl Acyl Sulfonamides as Efficient and Selective Na V 1.7 Inhibitors

DiMauro, E. F., Altmann, S. M., Berry, L., Bregman, H. S., Chakka, N., Chu‐Moyer, M. Y., Bojić, E. F., Foti, R., Fremeau, R. T., Gao, H., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00425 · Cited by 44 · see citing works

A structural atlas of druggable sites on Na v channels

Li, Z., Wu, Q., & Yan, N. (2023) · Channels · doi:10.1080/19336950.2023.2287832 · Cited by 44 · see citing works

Inhibitors of voltage-gated Sodium Channel Na v 1.7: Patent Applications Since 2010

Sun, S., Cohen, C. J., & Dehnhardt, C. M. (2014) · Pharmaceutical Patent Analyst · doi:10.4155/ppa.14.39 · Cited by 43 · see citing works

Voltage‐gated sodium channels: (NaV)igating the field to determine their contribution to visceral nociception

Erickson, A., Deiteren, A., Harrington, A. M., Garcia‐Caraballo, S., Castro, J., Caldwell, A., Grundy, L., & Brierley, S. M. (2018) · The Journal of Physiology · doi:10.1113/jp273461 · Cited by 42 · see citing works

Discovery of a selective, state-independent inhibitor of NaV1.7 by modification of guanidinium toxins

Pajouhesh, H., Beckley, J. T., Delwig, A., Hajare, H. S., Luu, G., Monteleone, D., Zhou, X., Ligutti, J., Amagasu, S. M., Moyer, B. D., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-71135-2 · Cited by 41 · see citing works

Towards Structure-Guided Development of Pain Therapeutics Targeting Voltage-Gated Sodium Channels

Nguyen, P. T., & Yarov-Yarovoy, V. M. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.842032 · Cited by 39 · see citing works

Pharmacology of the Na v 1.1 domain IV voltage sensor reveals coupling between inactivation gating processes

Osteen, J. D., Sampson, K. J., Iyer, V., Julius, D. J., & Bosmans, F. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1621263114 · Cited by 40 · see citing works

Development of New Benzenesulfonamides As Potent and Selective Na v 1.7 Inhibitors for the Treatment of Pain

Wu, Y., Guernon, J. M., Shi, J., Ditta, J. L., Robbins, K. J., Rajamani, R., Easton, A. E., Newton, A. E., Bourin, C., Mosure, K. W., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01918 · Cited by 39 · see citing works

Selective Ligands and Drug Discovery Targeting the Voltage-Gated Sodium Channel Nav1.7

Payandeh, J., & Hackos, D. H. (2018) · Handbook of experimental pharmacology · doi:10.1007/164_2018_97 · Cited by 39 · see citing works

Rat Na V 1.7 loss-of-function genetic model: Deficient nociceptive and neuropathic pain behavior with retained olfactory function and intra-epidermal nerve fibers

Grubinska, B., Chen, L., Alsaloum, M., Rampal, N., Matson, D. J., Yang, C., Taborn, K., Zhang, M., Youngblood, B. D., Liu, D., et al. (2019) · Molecular Pain · doi:10.1177/1744806919881846 · Cited by 39 · see citing works

Mechanisms Underlying the Selective Therapeutic Efficacy of Carbamazepine for Attenuation of Trigeminal Nerve Injury Pain

Pineda-Farías, J. B., Loeza‐Alcocer, E., Nagarajan, V., Gold, M. S., & Sekula, R. F. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.0547-21.2021 · Cited by 38 · see citing works

Size does matter! Label-free detection of small molecule–protein interaction

Fechner, P., Bleher, O., Ewald, M., Freudenberger, K., Furin, D., Hilbig, U., Kolarov, F., Krieg, K., Leidner, L., Markovic, G., et al. (2014) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-014-7834-4 · Cited by 38 · see citing works

The discovery of benzenesulfonamide-based potent and selective inhibitors of voltage-gated sodium channel Nav1.7

Sun, S., Jia, Q., Zenova, A., Chafeev, M. A., Zhang, Z., Lin, S., Kwan, R., Grimwood, M. E., Chowdhury, S., Young, C., et al. (2014) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2014.08.017 · Cited by 38 · see citing works

On the role of water density fluctuations in the inhibition of a proton channel

Gianti, E., Delemotte, L., Klein, M. L., & Carnevale, V. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1609964114 · Cited by 38 · see citing works

Understanding the Psychological, Physiological, and Genetic Factors Affecting Precision Pain Medicine: A Narrative Review

Chadwick, A. L., Frazier, A., Khan, T. W., & Young, E. E. (2021) · Journal of Pain Research · doi:10.2147/jpr.s320863 · Cited by 40 · see citing works

Benzoxazolinone aryl sulfonamides as potent, selective Nav1.7 inhibitors with in vivo efficacy in a preclinical pain model

Pero, J. E., Rossi, M., Lehman, H. D. G. F., Kelly, M. J., Mulhearn, J. J., Wolkenberg, S. E., Cato, M. J., Clements, M. K., Daley, C. J., Filzen, T. M., et al. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.04.040 · Cited by 37 · see citing works

G p T x‐1 and [ A la5, P he6, L eu26, A rg28] G p T x‐1, two peptide N aV1.7 inhibitors: analgesic and tolerance properties at the spinal level

Chen, C., Xu, B., Shi, X., Zhang, M., Zhang, Q., Zhang, T., Zhao, W., Zhang, R., Wang, Z., Li, N., et al. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14461 · Cited by 37 · see citing works

Downregulation of M Current Is Coupled to Membrane Excitability in Sympathetic Neurons Before the Onset of Hypertension

Davis, H., Herring, N., & Paterson, D. J. (2020) · Hypertension · doi:10.1161/hypertensionaha.120.15922 · Cited by 37 · see citing works

Structural basis for NaV1.7 inhibition by pore blockers

Zhang, J., Shi, Y., Huang, Z., Li, Y., Yang, B., Gong, J., & Jiang, D. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00860-1 · Cited by 37 · see citing works

Small molecule targeting NaV1.7 via inhibition of the CRMP2-Ubc9 interaction reduces and prevents pain chronification in a mouse model of oxaliplatin-induced neuropathic pain

Braden, K., Stratton, H. J., Salvemini, D., & Khanna, R. (2021) · Neurobiology of Pain · doi:10.1016/j.ynpai.2021.100082 · Cited by 36 · see citing works

Voltage-gated sodium channels viewed through a structural biology lens

Clairfeuille, T., Xu, H., Koth, C. M., & Payandeh, J. (2016) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2016.11.022 · Cited by 35 · see citing works

Identification of CNS-Penetrant Aryl Sulfonamides as Isoform-Selective NaV1.6 Inhibitors with Efficacy in Mouse Models of Epilepsy

Focken, T., Burford, K., Grimwood, M., Zenova, A., Andrez, J., Gong, W., Wilson, M., Taron, M., Decker, S., Lofstrand, V., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01032 · Cited by 35 · see citing works

IUPHAR review: Navigating the role of preclinical models in pain research

Karimi, S. A., Zahra, F. T., & Martin, L. J. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107073 · Cited by 35 · see citing works

Mechanism-specific assay design facilitates the discovery of Nav1.7-selective inhibitors

Chernov-Rogan, T., Li, T., Lu, G., Verschoof, H., Khakh, K., Jones, S. W., Beresini, M. H., Liu, C., Ortwine, D. F., McKerrall, S. J., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1713701115 · Cited by 34 · see citing works

Nuclear Factor-kappaB Gates Nav1.7 Channels in DRG Neurons via Protein-Protein Interaction

Xie, M.-X., Zhang, X., Xu, J., Zeng, W., Li, D., Xu, T., Pang, R., Ma, K., & Liu, X. (2019) · iScience · doi:10.1016/j.isci.2019.08.017 · Cited by 34 · see citing works

Antinociceptive properties of an isoform-selective inhibitor of Nav1.7 derived from saxitoxin in mouse models of pain

Beckley, J. T., Pajouhesh, H., Luu, G., Klas, S., Delwig, A., Monteleone, D., Zhou, X., Giuvelis, D., Meng, I. D., Yeomans, D. C., et al. (2020) · Pain · doi:10.1097/j.pain.0000000000002112 · Cited by 34 · see citing works

Molecular Pharmacology of Selective Na V 1.6 and Dual Na V 1.6/Na V 1.2 Channel Inhibitors that Suppress Excitatory Neuronal Activity Ex Vivo

Goodchild, S. J., Shuart, N. G., Williams, A. D., Ye, W., Parrish, R. R., Soriano, M., Thouta, S., Mezeyova, J., Waldbrook, M., Dean, R. A., et al. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00757 · Cited by 33 · see citing works

Tetrodotoxin-Sensitive Sodium Channels Mediate Action Potential Firing and Excitability in Menthol-Sensitive Vglut3-Lineage Sensory Neurons

Griffith, T. N., Docter, T. A., & Lumpkin, E. A. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.2817-18.2019 · Cited by 33 · see citing works

Thermally induced neuronal plasticity in the hypothalamus mediates heat tolerance

Ambroziak, W., Nencini, S., Pohle, J., Zuza, K., Pino, G., Lundh, S. H., Araujo-Sousa, C., Goetz, L. I. L., Schrenk-Siemens, K., Manoj, G., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01830-0 · Cited by 35 · see citing works

Suzetrigine: A Novel Non-Opioid Analgesic for Acute Pain Management—A Review

Jones, M., Demery, A., & Al‐Horani, R. A. (2025) · Drugs and Drug Candidates · doi:10.3390/ddc4030032 · Cited by 31 · see citing works

PACAP-Induced PAC1 Receptor Internalization and Recruitment of Endosomal Signaling Regulate Cardiac Neuron Excitability

Parsons, R. L., & May, V. (2018) · Journal of Molecular Neuroscience · doi:10.1007/s12031-018-1127-x · Cited by 31 · see citing works

Novel sodium channel antagonists in the treatment of neuropathic pain

Rivara, M., & Zuliani, V. (2015) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2016.1121992 · Cited by 30 · see citing works

Progress and challenges in the optimization of toxin peptides for development as pain therapeutics

Netirojjanakul, C., & Miranda, L. P. (2017) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2017.03.004 · Cited by 30 · see citing works

Cryo-EM reveals an unprecedented binding site for NaV1.7 inhibitors enabling rational design of potent hybrid inhibitors

Kschonsak, M., Jao, C. C., Arthur, C. P., Rohou, A. L., Bergeron, P., Ortwine, D. F., McKerrall, S. J., Hackos, D. H., Deng, L., Chen, J., et al. (2023) · eLife · doi:10.7554/elife.84151 · Cited by 30 · see citing works

Design of Conformationally Constrained Acyl Sulfonamide Isosteres: Identification ofN-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)methane-sulfonamides as Potent and SelectivehNaV1.7 Inhibitors for the Treatment of Pain

Focken, T., Chowdhury, S., Zenova, A., Grimwood, M., Chabot, C., Sheng, T., Hemeon, I., Decker, S., Wilson, M., Bichler, P., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01826 · Cited by 30 · see citing works

Drug Development in Channelopathies: Allosteric Modulation of Ligand-Gated and Voltage-Gated Ion Channels

Zhang, Y., Wang, K., & Yu, Z. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01304 · Cited by 29 · see citing works

Activation of MEK/ERK signaling contributes to the PACAP-induced increase in guinea pig cardiac neuron excitability

Tompkins, J. D., Clason, T. A., Hardwick, J. C., Girard, B. M., Merriam, L. A., May, V., & Parsons, R. L. (2016) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00164.2016 · Cited by 29 · see citing works

Highly potent and selective NaV1.7 inhibitors for use as intravenous agents and chemical probes

Storer, R. I., Pike, A., Swain, N. A., Alexandrou, A. J., Bechle, B. M., Blakemore, D. C., Brown, A. D., Castle, N. A., Corbett, M. S., Flanagan, N. J., et al. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.09.056 · Cited by 28 · see citing works

Fibroblast growth factor homologous factors serve as a molecular rheostat in tuning arrhythmogenic cardiac late sodium current

Chakouri, N., Rivas, S., Roybal, D., Yang, L., Diaz, J., Hsu, A. L., Mahling, R. W., Chen, B.-X., Owoyemi, J. O., DiSilvestre, D. A., et al. (2022) · Nature Cardiovascular Research · doi:10.1038/s44161-022-00060-6 · Cited by 28 · see citing works

Structural basis of Nav1.7 inhibition by an isoform-selective small-molecule antagonist

Ahuja, S., Mukund, S., Deng, L., Khakh, K., Chang, E., Ho, H., Shriver, S., Young, C., Lin, S., Johnson, J. P., et al. (2015) · Science · doi:10.1126/science.aac5464 · Cited by 319 · see citing works

Identification and characterization of selective inhibitors of Nav1.9 voltage dependent sodium channels

Potet, F., Santos, S., Gallucci, A., Theile, J. W., Yoger, K., Lin, Z., Lebreton, S., Volkmann, R., Dow, R., Elban, M. A., et al. (2026) · Molecular Pharmacology · doi:10.1016/j.molpha.2026.100125

The tarantula toxin β/δ-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity

Wingerd, J. S., Mozar, C. A., Ussing, C. A., Murali, S. S., Chin, Y. K. ‐., Cristofori‐Armstrong, B., Durek, T., Gilchrist, J. M., Vaughan, C. W., Bosmans, F., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-01129-0 · Cited by 21 · see citing works

Deconstructing voltage sensor function and pharmacology in sodium channels

Bosmans, F., Martin‐Eauclaire, M., & Swartz, K. J. (2008) · Nature · doi:10.1038/nature07473 · Cited by 261 · see citing works

Using Potassium Channels As Reporters To Deconstruct The Function And Pharmacology Of Sodium Channel Voltage Sensors

Bosmans, F., Martin‐Eauclaire, M., & Swartz, K. J. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2008.12.961