Target family: Voltage-gated sodium channels (Na<sub>V</sub>) (type: vgic)
Target: Na<sub>v</sub>1.2

Ligand: aconitine (Natural product)
Interaction type: Activator
Action: Partial agonist
Ligand approved: no
Primary target: no
Median affinity: 5.900000095367432 pKd
Reference (Journal): Binding of batrachotoxinin A 20-alpha-benzoate to a receptor site associated with sodium channels in synaptic nerve ending particles.
Published in: J Biol Chem

Ligand: AFT-II (Peptide)
Interaction type: Gating inhibitor
Action: Slows inactivation
Ligand approved: no
Primary target: no
Median affinity: 5.699999809265137 pEC50
Reference (Journal): Binding specificity of sea anemone toxins to Nav 1.1-1.6 sodium channels: unexpected contributions from differences in the IV/S3-S4 outer loop.
Published in: J Biol Chem

Ligand: α-scorpion toxin 2 (Peptide)
Interaction type: Gating inhibitor
Action: Slows inactivation
Ligand approved: no
Primary target: no
Median affinity: 9.100000381469727 pEC50
Reference (Journal): Combinatorial interaction of scorpion toxins Lqh-2, Lqh-3, and LqhalphaIT with sodium channel receptor sites-3.
Published in: Mol Pharmacol

Ligand: α-scorpion toxin 2 (Peptide)
Interaction type: Gating inhibitor
Action: Slows inactivation
Ligand approved: no
Primary target: no
Median affinity: 8.699999809265137 pKd
Reference (Journal): Molecular determinants of high affinity binding of alpha-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na+ channel alpha subunit.
Published in: J Biol Chem

Ligand: ATX-II (Peptide)
Interaction type: Gating inhibitor
Action: Slows inactivation
Ligand approved: no
Primary target: no
Median affinity: 8.100000381469727 pEC50
Reference (Journal): Binding specificity of sea anemone toxins to Nav 1.1-1.6 sodium channels: unexpected contributions from differences in the IV/S3-S4 outer loop.
Published in: J Biol Chem

Ligand: batrachotoxin (Natural product)
Interaction type: Activator
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity: 9.100000381469727 pKd
Reference (Journal): Interaction of batrachotoxin with the local anesthetic receptor site in transmembrane segment IVS6 of the voltage-gated sodium channel.
Published in: Proc Natl Acad Sci USA

Ligand: Bc-III (Peptide)
Interaction type: Gating inhibitor
Action: Slows inactivation
Ligand approved: no
Primary target: no
Median affinity: 5.800000190734863 pEC50
Reference (Journal): Binding specificity of sea anemone toxins to Nav 1.1-1.6 sodium channels: unexpected contributions from differences in the IV/S3-S4 outer loop.
Published in: J Biol Chem

Ligand: β-scorpion toxin Css IV (Peptide)
Interaction type: Activator
Action: Partial agonist
Ligand approved: no
Median affinity: 9.7 pKd
Reference (Journal): Voltage sensor-trapping: enhanced activation of sodium channels by beta-scorpion toxin bound to the S3-S4 loop in domain II.
Published in: Neuron

Ligand: δ-hexatoxin-Mg1a (Peptide)
Interaction type: Gating inhibitor
Action: Slows inactivation
Ligand approved: no
Primary target: no
Median affinity: 4.5 pEC50
Reference (Journal): Synthesis, solution structure, and phylum selectivity of a spider delta-toxin that slows inactivation of specific voltage-gated sodium channel subtypes.
Published in: J Biol Chem

Ligand: etidocaine (Synthetic organic)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: no
Primary target: no
Median affinity: 6 pIC50
Reference (Journal): Molecular determinants of state-dependent block of Na+ channels by local anesthetics.
Published in: Science

Ligand: funapide (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.21999979019165 pIC50
Reference (Journal): Challenges and Opportunities for Therapeutics Targeting the Voltage-Gated Sodium Channel Isoform Na<sub>V</sub>1.7.
Published in: J Med Chem

Ligand: GNE-131 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.149999618530273 pIC50
Reference (Journal): Design of Conformationally Constrained Acyl Sulfonamide Isosteres: Identification of N-([1,2,4]Triazolo[4,3- a]pyridin-3-yl)methane-sulfonamides as Potent and Selective hNa<sub>V</sub>1.7 Inhibitors for the Treatment of Pain.
Published in: J Med Chem

Ligand: GNE-616 (Synthetic organic)
Interaction type: Channel blocker
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.920000076293945 pKd
Reference (Journal): Structure- and Ligand-Based Discovery of Chromane Arylsulfonamide Na<sub>v</sub>1.7 Inhibitors for the Treatment of Chronic Pain.
Published in: J Med Chem

Ligand: huwentoxin IV (Peptide)
Interaction type: Gating inhibitor
Action: Voltage-dependent inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.800000190734863 pKd
Reference (Journal): Analysis of the structural and molecular basis of voltage-sensitive sodium channel inhibition by the spider toxin huwentoxin-IV (μ-TRTX-Hh2a).
Published in: J Biol Chem

Ligand: lacosamide (Synthetic organic)
Interaction type: Channel blocker
Action: Antagonist
Ligand approved: yes
Approval source: EMA and FDA (2008)
Primary target: no
Median affinity: 4.519999980926514 pIC50
Reference (Journal): A thermosensitive mutation alters the effects of lacosamide on slow inactivation in neuronal voltage-gated sodium channels, NaV1.2.
Published in: Front Pharmacol

Ligand: lamotrigine (Synthetic organic)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: yes
Approval source: FDA (1994)
Primary target: no
Median affinity: 4.5 pIC50
Reference (Journal): Differential interactions of lamotrigine and related drugs with transmembrane segment IVS6 of voltage-gated sodium channels.
Published in: Neuropharmacology

Ligand: lamotrigine (Synthetic organic)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: yes
Approval source: FDA (1994)
Primary target: no
Median affinity: 4.5 pIC50
Reference (Journal): Interaction of the antiepileptic drug lamotrigine with recombinant rat brain type IIA Na+ channels and with native Na+ channels in rat hippocampal neurones.
Published in: Pflugers Arch

Ligand: lidocaine (Synthetic organic)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: yes
Approval source: FDA (1948)
Primary target: no
Median affinity: 5 pIC50
Reference (Journal): Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels.
Published in: Proc Natl Acad Sci USA

Ligand: μ-conotoxin SmIIIA (Peptide)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: no
Primary target: no
Median affinity: 8.899999618530273 pKd
Reference (Journal): μ-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve.
Published in: Proc Natl Acad Sci USA

Ligand: phenytoin (Synthetic organic)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: yes
Approval source: FDA (1953)
Primary target: yes
Median affinity: 4.900000095367432 pIC50
Reference (Journal): Frequency and voltage-dependent inhibition of type IIA Na+ channels, expressed in a mammalian cell line, by local anesthetic, antiarrhythmic, and anticonvulsant drugs.
Published in: Mol Pharmacol

Ligand: phenytoin (Synthetic organic)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: yes
Approval source: FDA (1953)
Primary target: no
Median affinity: 4.699999809265137 pIC50
Reference (Journal): Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels.
Published in: Proc Natl Acad Sci USA

Ligand: protoxin II (Peptide)
Interaction type: Gating inhibitor
Action: Voltage-dependent inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.400000095367432 pKi
Reference (Journal): ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors.
Published in: Mol Pharmacol

Ligand: relutrigine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.760000228881836 pIC50
Reference (Journal): The novel persistent sodium current inhibitor PRAX-562 has potent anticonvulsant activity with improved protective index relative to standard of care sodium channel blockers.
Published in: Epilepsia

Ligand: saxitoxin (Natural product)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: no
Primary target: no
Median affinity: 8.800000190734863 pIC50
Reference (Journal): Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSP.
Published in: Nature

Ligand: tetrodotoxin (Natural product)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: no
Primary target: no
Median affinity: 8 pIC50
Reference (Journal): Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSP.
Published in: Nature

Ligand: veratridine (Natural product)
Interaction type: Activator
Action: Partial agonist
Ligand approved: no
Primary target: no
Median affinity: 5.199999809265137 pKd
Reference (Journal): Binding of batrachotoxinin A 20-alpha-benzoate to a receptor site associated with sodium channels in synaptic nerve ending particles.
Published in: J Biol Chem

Ligand: XPC-5462 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.960000038146973 pIC50
Reference (Journal): Molecular Pharmacology of Selective Na<sub>V</sub>1.6 and Dual Na<sub>V</sub>1.6/Na<sub>V</sub>1.2 Channel Inhibitors that Suppress Excitatory Neuronal Activity Ex Vivo.
Published in: ACS Chem Neurosci