Target family: Voltage-gated sodium channels (Na<sub>V</sub>) (type: vgic)
Target: Na<sub>v</sub>1.5

Ligand: veratridine (Natural product)
Interaction type: Activator
Action: Partial agonist
Ligand approved: no
Primary target: no
Median affinity: 6.300000190734863 pEC50
Reference (Journal): Sodium channel comodification with full activator reveals veratridine reaction dynamics.
Published in: Mol Pharmacol

Ligand: tetrodotoxin (Natural product)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: no
Primary target: no
Median affinity: 5.800000190734863 pKd
Reference (Journal): Functional expression of the rat heart I Na+ channel isoform. Demonstration of properties characteristic of native cardiac Na+ channels.
Published in: FEBS Lett

Ligand: tetrodotoxin (Natural product)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: no
Primary target: no
Median affinity: 5.800000190734863 pKd
Reference (Journal): Cardiac sodium channels expressed in a peripheral neurotumor-derived cell line, RT4-B8.
Published in: Am J Physiol

Ligand: saxitoxin (Natural product)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: no
Primary target: no
Median affinity: 7.400000095367432 pKd
Reference (Journal): Cardiac sodium channels expressed in a peripheral neurotumor-derived cell line, RT4-B8.
Published in: Am J Physiol

Ligand: saxitoxin (Natural product)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: no
Primary target: no
Median affinity: 7.400000095367432 pKd
Reference (Journal): Functional expression of the rat heart I Na+ channel isoform. Demonstration of properties characteristic of native cardiac Na+ channels.
Published in: FEBS Lett

Ligand: ropivacaine (Synthetic organic)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: yes
Approval source: FDA (1996)
Primary target: no
Median affinity: 4.559999942779541 pIC50
Reference (Journal): A Comparative Analysis of Bupivacaine and Ropivacaine Effects on Human Cardiac SCN5A Channels.
Published in: Anesth Analg

Ligand: ropivacaine (Synthetic organic)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: yes
Approval source: FDA (1996)
Primary target: no
Median affinity: 3.490000009536743 pIC50
Reference (Journal): A Comparative Analysis of Bupivacaine and Ropivacaine Effects on Human Cardiac SCN5A Channels.
Published in: Anesth Analg

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: quinidine (Natural product)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: yes
Approval source: FDA (1950)
Primary target: no
Median affinity:  pIC50
Reference (Journal): Class I antiarrhythmic drugs: allosteric inhibitors of [3H] batrachotoxinin binding to rat cardiac sodium channels.
Published in: J Pharmacol Exp Ther

Ligand: quinidine (Natural product)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: yes
Approval source: FDA (1950)
Primary target: no
Median affinity:  pIC50
Reference (Journal): Class I antiarrhythmic drug receptor: biochemical evidence for state-dependent interaction with quinidine and lidocaine.
Published in: Mol Pharmacol

Ligand: protoxin II (Peptide)
Interaction type: Gating inhibitor
Action: Voltage-dependent inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.5 pKi
Reference (Journal): Two tarantula peptides inhibit activation of multiple sodium channels.
Published in: Biochemistry

Ligand: μ-conotoxin SmIIIA (Peptide)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: no
Primary target: no
Median affinity: 5.5 pKi
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: lidocaine (Synthetic organic)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: yes
Approval source: FDA (1948)
Primary target: no
Median affinity: 4.199999809265137 pIC50
Reference (Journal): Class I antiarrhythmic drug receptor: biochemical evidence for state-dependent interaction with quinidine and lidocaine.
Published in: Mol Pharmacol

Ligand: lidocaine (Synthetic organic)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: yes
Approval source: FDA (1948)
Primary target: yes
Median affinity: 4.800000190734863 pKd
Reference (Journal): Cardiac sodium channels (hH1) are intrinsically more sensitive to block by lidocaine than are skeletal muscle (mu 1) channels.
Published in: J Gen Physiol

Ligand: jingzhaotoxin-III (Peptide)
Interaction type: Gating inhibitor
Action: Voltage-dependent inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.5 pKi
Reference (Journal): Molecular basis of the tarantula toxin jingzhaotoxin-III (β-TRTX-Cj1α) interacting with voltage sensors in sodium channel subtype Nav1.5.
Published in: FASEB J

Ligand: GS-458967 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.889999866485596 pIC50
Reference (Journal): Selective late sodium current inhibitor GS-458967 suppresses Torsades de Pointes by mostly affecting perpetuation but not initiation of the arrhythmia.
Published in: Br J Pharmacol

Ligand: GNE-616 (Synthetic organic)
Interaction type: Channel blocker
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6 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: GNE-131 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.960000038146973 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: funapide (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.079999923706055 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: eleclazine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity:  -
Reference (Patent): Compound and methods for treating long qt syndrome.

Ligand: bupivacaine (Synthetic organic)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: yes
Approval source: FDA (1972), EMA (2020)
Primary target: no
Median affinity: 5.659999847412109 pIC50
Reference (Journal): A Comparative Analysis of Bupivacaine and Ropivacaine Effects on Human Cardiac SCN5A Channels.
Published in: Anesth Analg

Ligand: bupivacaine (Synthetic organic)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: yes
Approval source: FDA (1972), EMA (2020)
Primary target: no
Median affinity: 4.159999847412109 pIC50
Reference (Journal): A Comparative Analysis of Bupivacaine and Ropivacaine Effects on Human Cardiac SCN5A Channels.
Published in: Anesth Analg

Ligand: Bc-III (Peptide)
Interaction type: Gating inhibitor
Action: Slows inactivation
Ligand approved: no
Primary target: no
Median affinity: 6.5 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: Full agonist
Ligand approved: no
Primary target: no
Median affinity: 7.599999904632568 pKd
Reference (Journal): Binding of [3H]batrachotoxinin A benzoate to specific sites on rat cardiac sodium channels.
Published in: Mol Pharmacol

Ligand: ATX-II (Peptide)
Interaction type: Gating inhibitor
Action: Slows inactivation
Ligand approved: no
Primary target: no
Median affinity: 7.300000190734863 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: amiodarone (Synthetic organic)
Interaction type: Channel blocker
Action: Pore blocker
Ligand approved: yes
Approval source: FDA (1985)
Primary target: no
Median affinity: 5.699999809265137 pIC50
Reference (Journal): Amiodarone: biochemical evidence for binding to a receptor for class I drugs associated with the rat cardiac sodium channel.
Published in: Circ Res

Ligand: AM-6120 (Peptide)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 5.179999828338623 pIC50
Reference (Journal): Discovery of Tarantula Venom-Derived Na<sub>V</sub>1.7-Inhibitory JzTx-V Peptide 5-Br-Trp24 Analogue AM-6120 with Systemic Block of Histamine-Induced Pruritis.
Published in: J Med Chem

Ligand: α-scorpion toxin 2 (Peptide)
Interaction type: Gating inhibitor
Action: Slows inactivation
Ligand approved: no
Primary target: no
Median affinity: 7.699999809265137 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: AFT-II (Peptide)
Interaction type: Gating inhibitor
Action: Slows inactivation
Ligand approved: no
Primary target: no
Median affinity: 7.199999809265137 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: aconitine (Natural product)
Interaction type: Activator
Action: Partial agonist
Ligand approved: no
Primary target: no
Median affinity:  -
Reference (Journal): Properties of aconitine-modified sodium channels in single cells of mouse ventricular myocardium.
Published in: Gen Physiol Biophys