SCN9A

Summary

SCN9A (sodium voltage-gated channel alpha subunit 9, HGNC:10597) is a protein-coding gene on chromosome 2q24.3, encoding Sodium channel protein type 9 subunit alpha (Q15858). Pore-forming subunit of Nav1.7, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.

This gene encodes a voltage-gated sodium channel which plays a significant role in nociception signaling. Mutations in this gene have been associated with primary erythermalgia, channelopathy-associated insensitivity to pain, and paroxysmal extreme pain disorder.

Source: NCBI Gene 6335 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary erythermalgia (Definitive, GenCC) — +7 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 1,619 total — 68 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 144
• Druggable target: yes — 36 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001365536

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10597
Approved symbol	SCN9A
Name	sodium voltage-gated channel alpha subunit 9
Location	2q24.3
Locus type	gene with protein product
Status	Approved
Aliases	Nav1.7, PN1, NE-NA, NENA, ETHA
Ensembl gene	ENSG00000169432
Ensembl biotype	protein_coding
OMIM	603415
Entrez	6335

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay

ENST00000303354, ENST00000409672, ENST00000452182, ENST00000454569, ENST00000472119, ENST00000642356, ENST00000643319, ENST00000645283, ENST00000645815, ENST00000645907, ENST00000646694, ENST00000667201, ENST00000667991

RefSeq mRNA: 2 — MANE Select: NM_001365536 NM_001365536, NM_002977

CCDS: CCDS46441, CCDS92892

Canonical transcript exons

ENST00000642356 — 27 exons

Exon	Start	End
ENSE00001128397	166204360	166204464
ENSE00001128404	166242502	166242656
ENSE00001128413	166280357	166280595
ENSE00001128421	166293231	166293372
ENSE00001128428	166294599	166294662
ENSE00001128443	166203955	166204225
ENSE00001128456	166227670	166227723
ENSE00001128459	166228691	166228972
ENSE00001128466	166233340	166233462
ENSE00001128471	166238094	166238267
ENSE00001128480	166251765	166251885
ENSE00001128485	166272399	166272875
ENSE00001128510	166281679	166281808
ENSE00001128517	166284453	166284824
ENSE00001128525	166286336	166286623
ENSE00001128530	166288437	166288643
ENSE00001129637	166303090	166303302
ENSE00001578488	166306510	166306599
ENSE00001584414	166311499	166311806
ENSE00001585608	166306956	166307074
ENSE00002474880	166278140	166278313
ENSE00002481484	166226567	166226704
ENSE00002495223	166276983	166277339
ENSE00003584389	166304238	166304329
ENSE00003608010	166305792	166305920
ENSE00003821670	166375697	166375944
ENSE00003901424	166195185	166199864

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 90.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.2336 / max 346.9374, expressed in 1043 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31685	5.8174	1005
31686	0.2405	107
31687	0.1757	76

Top tissues by expression

278 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	90.90	gold quality
dorsal root ganglion	UBERON:0000044	88.05	gold quality
stromal cell of endometrium	CL:0002255	83.65	gold quality
trigeminal ganglion	UBERON:0001675	80.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.17	gold quality
calcaneal tendon	UBERON:0003701	77.85	gold quality
colonic epithelium	UBERON:0000397	77.13	gold quality
tibial nerve	UBERON:0001323	76.87	gold quality
right lobe of liver	UBERON:0001114	76.30	gold quality
right testis	UBERON:0004534	76.06	gold quality
left testis	UBERON:0004533	75.05	gold quality
cortical plate	UBERON:0005343	74.81	gold quality
muscle layer of sigmoid colon	UBERON:0035805	74.14	gold quality
rectum	UBERON:0001052	73.63	gold quality
testis	UBERON:0000473	73.52	gold quality
hypothalamus	UBERON:0001898	73.45	gold quality
transverse colon	UBERON:0001157	73.15	gold quality
islet of Langerhans	UBERON:0000006	72.88	gold quality
sigmoid colon	UBERON:0001159	72.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.97	gold quality
body of pancreas	UBERON:0001150	71.91	gold quality
spleen	UBERON:0002106	71.79	gold quality
mucosa of transverse colon	UBERON:0004991	71.52	gold quality
pancreas	UBERON:0001264	71.36	gold quality
colon	UBERON:0001155	71.28	gold quality
large intestine	UBERON:0000059	70.89	gold quality
liver	UBERON:0002107	69.88	gold quality
intestine	UBERON:0000160	68.98	gold quality
tendon	UBERON:0000043	66.32	gold quality
bone marrow cell	CL:0002092	65.75	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	13.03
E-CURD-114	yes	10.03
E-ANND-3	yes	8.78
E-HCAD-25	yes	7.88
E-GEOD-81383	no	129.85

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ESR1, ESR2, IL10, NGF, POU4F1, TNF, USF1

miRNA regulators (miRDB)

226 targeting SCN9A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-568	99.98	69.86	2084

Literature-anchored findings (GeneRIF, showing 40)

• mutations in SCN9A cause primary erythermalgia (PMID:14985375)
• We show that mutations in Na(v)1.7 associated with erythermalgia produce a hyperpolarizing shift in activation and slow deactivation, and cause an increased amplitude of the current produced by Na(v)1.7 in response to slow, small polarizations (PMID:15385606)
• familial erythromelalgia is a channelopathy caused by mutations in the gene encoding the Na(v)1.7 sodium channel which lead to altered channel function (PMID:15929046)
• detected missense sequence variants in SCN9A to be present in primary erythermalgia patients (PMID:15955112)
• Nav1.7 is the VGSCalpha most strikingly upregulated (approximately 20-fold) in prostate neoplasms (PMID:16088330)
• primary erythermalgia may be caused by hyperexcitability of nav1.7. (PMID:16216943)
• A single amino acid substitution (L858F) in the DIIS4-S5 linker of Na(v)1.7 was present in two children whose parents were asymptomatic. The asymptomatic father was genetically mosaic for the mutation. (PMID:16392115)
• These results provide a physiologic basis for the linkage to erythermalgia of an Na(v)1.7 mutation that substitutes one uncharged residue for another within an S4 segment of the channel. (PMID:16988069)
• the linker between S4 and S5 in domain I of Nav1.7 modulates gating of this channel, and a larger side chain at position 241 interferes with its gating mechanisms (PMID:17008310)
• Ala863Pro mutant Nav1.7 channels produce hyperexcitability in dorsal root ganglia neurons, which contributes to the pathophysiology of erythromelalgia/erythermalgia. (PMID:17135418)
• An SCN9A channelopathy causes congenital inability to experience pain (PMID:17167479)
• data suggest that SCN9A is an essential and non-redundant requirement for nociception in humans (PMID:17167479)
• A Taiwanese family with the characteristic features of erythromelalgia is described. Genetic linkage studies established that the disease locus maps to human chromosome 2 and a novel mutation SCN9A(I136V) (PMID:17294067)
• results suggest that the enhancement of TTX-sensitive sodium current density in differentiated NG108-15 cells is mainly due to the increase in the expression of the TTX-sensitive voltage-gated Na+ channel, NaV1.7 (PMID:17404832)
• A patient represents a typical case of juvenile onset primary familial erythromelalgia, a rare disorder that has been shown in some patients to be caused by a mutation to the SCN9A gene. (PMID:17410110)
• Mutations in SCN9A may mediate variabiilty in lidocaine sensitivity in erythromelalgia patients. (PMID:17430993)
• identified 10 mutations in the SCN9A gene encoding the sodium channel protein Nav1.7 in congenital indifference to pain (PMID:17470132)
• A stop codon mutation in SCN9A causes lack of pain sensation. (PMID:17597096)
• In rectal hypersensitivity, Na(v)1.7 immunoreactive nerve fibres were significantly increased in mucosal, sub-mucosal, and muscle layers (PMID:17928139)
• The contribution of Na(v)1.7 to acquired and inherited pain states and the absence of motor, cognitive and cardiac deficits in patients lacking this channel make it an attractive target for the treatment of neuropathic pain. (PMID:17950472)
• This study describe a boy with erythermalgia whose painful attacks began in infancy. We found a novel mutation of SCN9A. (PMID:17985268)
• VGSC activity has a significant intermediary role in potentiating effect of EGF in human prostate cancer (PMID:18036246)
• highlights of recent developments and discussion of the critical role of Na(v)1.7 in pain sensation in humans [review] (PMID:18060017)
• review: a series of SCN9A mutations resulting in gain-of-function phenotypes presenting with the phenotype of enhanced pain sensitivity. (PMID:18070139)
• review: Congenital Indifference to Pain patients assessed are homozygous or compound heterozygous for nonsense mutations at various locations throughout SCN9A, resulting in an early stop codon (PMID:18070140)
• State- and use-dependent block of neuronal Nav1.7 voltage-gated Na+ channel isoforms by ranolazine is reported. (PMID:18079277)
• The isoleucine-136-valine substitution alters channel gating and kinetic properties, contributing to erythromelalgia. (PMID:18171466)
• alternative splicing of human Na(v)1.7 can specifically modulate the biophysical properties and cAMP-mediated regulation of this channel (PMID:18337362)
• We detected a low SCN9A mutation rate in patients with primary erythermalgia suggesting that pain syndromes in the skin may have a polygenic basis (PMID:18347287)
• the increased axonal expression and augmentation of Nav1.7 at intact and remodeling/demyelinating nodes within the painful human dental pulp (PMID:18426592)
• variations of SCN9A can lead to complete inability to sense pain (PMID:18439623)
• two missense mutations in Nav1.7 in a family with erythermalgia; one of the two variants (L858F) is causal for erythermalgia; the second variant (P610T) may modify the phenotype (PMID:18518989)
• This study demonstrated that mutations within D3/S4-S5 affect inactivation of Nav1.7 in a residue-specific manner and disruption of the fast-inactivated state by these mutations can be more moderate than previously indicated. (PMID:18599537)
• Met1627Lys mutant SCN9A channels render dorsal root ganglion neurons hyperexcitable and provide a link between altered channel biophysics and pain in paroxysmal extreme pain disorder. (PMID:18803825)
• Erythromelalgia and paroxysmal extreme pain disorder mutants(Nav1.7 A1632E)are part of a physiological continuum that can produce a continuum of clinical phenotypes. (PMID:18945915)
• Na(V)1.7 is expressed in aorta after balloon injury, suggesting a potential role for Na(V)1.7 in the progression of intimal hyperplasia (PMID:18978189)
• Here we describe a woman with insensitivity to pain with two novel mutations in the SCN9A gene, coding for the Nav1.7 channel. (PMID:19304393)
• study reports a novel Nav1.7 mutation (V400M) in a three-generation Canadian family with inherited erythromelalgia in which pain is relieved by carbamazepine (PMID:19557861)
• the additive effects observed on ramp currents from exon 5 splicing and the PEPD mutation (I1461T) are likely to impact the disease phenotype (PMID:19633428)
• In trigeminal neuralgia (TN) there is a reduction in the expression of Nav1.7 and an increase in the expression of Nav1.3, Nav1.8 expression not significantly different; TN can be, at least in part, a channelopathy. (PMID:19699781)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Scn9a	ENSMUSG00000075316
rattus_norvegicus	Scn9a	ENSRNOG00000006639

Paralogs (26): CACNA1G (ENSG00000006283), SCN4A (ENSG00000007314), CACNA1S (ENSG00000081248), CACNA1I (ENSG00000100346), CACNA1F (ENSG00000102001), NALCN (ENSG00000102452), SCN2A (ENSG00000136531), SCN7A (ENSG00000136546), CACNA1A (ENSG00000141837), SCN1A (ENSG00000144285), CACNA1B (ENSG00000148408), CACNA1C (ENSG00000151067), CATSPER3 (ENSG00000152705), SCN3A (ENSG00000153253), CACNA1D (ENSG00000157388), TPCN2 (ENSG00000162341), CATSPER2 (ENSG00000166762), SCN11A (ENSG00000168356), CATSPER1 (ENSG00000175294), SCN5A (ENSG00000183873), SCN10A (ENSG00000185313), TPCN1 (ENSG00000186815), CATSPER4 (ENSG00000188782), CACNA1H (ENSG00000196557), SCN8A (ENSG00000196876), CACNA1E (ENSG00000198216)

Protein

Protein identifiers

Sodium channel protein type 9 subunit alpha — Q15858 (reviewed: Q15858)

Alternative names: Neuroendocrine sodium channel, Peripheral sodium channel 1, Sodium channel protein type IX subunit alpha, Voltage-gated sodium channel subunit alpha Nav1.7

All UniProt accessions (7): A0A0C4DG82, A0A2R8Y7G0, A0A2R8YCX9, A0A590UJB2, A0A590UK23, Q15858, H7C064

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming subunit of Nav1.7, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues. Nav1.7 plays a crucial role in controlling the excitability and action potential propagation from nociceptor neurons, thereby contributing to the sensory perception of pain.

Subunit / interactions. The Nav1.7 voltage-gated sodium channel consists of an ion-conducting alpha subunit SCN9A which is functional on its own regulated by one or more beta-1 (SCN1B), beta-2 (SCN2B), beta-3 (SCN3B) and beta-4 (SCN4B) subunits. SCN1B and SCN3B are non-covalently associated with SCN9A. SCN2B and SCN4B are disulfide-linked to SCN9A. SCN1B regulates channel inactivation. Interacts with NEDD4 and NEDD4L; regulates Nav1.7 activity most probably through ubiquitination and subsequent endocytosis. Interacts with TMEM233; modulates the gating properties of NaV1.7.

Subcellular location. Cell membrane. Cell projection. Neuron projection. Axon.

Tissue specificity. Expressed strongly in dorsal root ganglion, with only minor levels elsewhere in the body, smooth muscle cells, MTC cell line and C-cell carcinoma. Also expressed in vagus nerves within the head and neck region. Isoform 1 is expressed preferentially in the central and peripheral nervous system. Isoform 2 is expressed preferentially in the dorsal root ganglion.

Post-translational modifications. Phosphorylation at Ser-1490 by PKC in a highly conserved cytoplasmic loop increases peak sodium currents. Ubiquitinated by NEDD4L; which may promote its endocytosis.

Disease relevance. Primary erythermalgia (PERYTHM) [MIM:133020] Autosomal dominant disease characterized by recurrent episodes of severe pain associated with redness and warmth in the feet or hands. The disease is caused by variants affecting the gene represented in this entry. Indifference to pain, congenital, autosomal recessive (CIP) [MIM:243000] A disorder characterized by congenital inability to perceive any form of pain, in any part of the body. All other sensory modalities are preserved and the peripheral and central nervous systems are apparently intact. Patients perceive the sensations of touch, warm and cold temperature, proprioception, tickle and pressure, but not painful stimuli. There is no evidence of a motor or sensory neuropathy, either axonal or demyelinating. The disease is caused by variants affecting the gene represented in this entry. Paroxysmal extreme pain disorder (PEXPD) [MIM:167400] An autosomal dominant paroxysmal disorder of pain and autonomic dysfunction. The distinctive features are paroxysmal episodes of burning pain in the rectal, ocular, and mandibular areas accompanied by autonomic manifestations such as skin flushing. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by tetrodotoxin. Weakly inhibited by saxitoxin. Inhibited by the spider huwentoxin-IV that binds the extracellular loop S3-S4 of repeat II. Inhibited by the spider protoxin-II that binds the extracellular loop S3-S4 of repeats II and IV. Inhibited by the scorpion alpha-toxins CvIV4 and AaH2. Inhibited by the conotoxin GVIIJ. Inhibited by the spider beta/delta-theraphotoxin-Pre1a.

Domain organisation. The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.

Similarity. Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.7/SCN9A subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q15858-1	1	yes
Q15858-2	2
Q15858-3	3
Q15858-4	4

RefSeq proteins (2): NP_001352465, NP_002968 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site
IPR001696	Na_channel_asu	Family
IPR005821	Ion_trans_dom	Domain
IPR010526	Na_trans_assoc_dom	Domain
IPR024583	Na_trans_cytopl	Domain
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR043203	VGCC_Ca_Na	Family
IPR044564	Na_chnl_inactivation_gate	Domain
IPR058542	IQ_SCN5A_C	Domain

Pfam: PF00520, PF06512, PF11933, PF24609

Catalyzed reactions (Rhea), 1 shown:

• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (291 total): helix 74, sequence variant 38, strand 35, topological domain 29, transmembrane region 24, mutagenesis site 21, turn 21, compositionally biased region 9, sequence conflict 8, disulfide bond 7, region of interest 5, glycosylation site 5, intramembrane region 4, repeat 4, site 2, splice variant 2, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

43 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8YHZ	X-RAY DIFFRACTION	1.62
7W9K	ELECTRON MICROSCOPY	2.2
8F0P	ELECTRON MICROSCOPY	2.2
8F0Q	ELECTRON MICROSCOPY	2.5
8I5Y	ELECTRON MICROSCOPY	2.6
21TQ	ELECTRON MICROSCOPY	2.7
7XVE	ELECTRON MICROSCOPY	2.7
8I5B	ELECTRON MICROSCOPY	2.7
8I5G	ELECTRON MICROSCOPY	2.7
8THH	ELECTRON MICROSCOPY	2.7
7XVF	ELECTRON MICROSCOPY	2.8
8G1A	ELECTRON MICROSCOPY	2.8
8XMM	ELECTRON MICROSCOPY	2.89
7W9P	ELECTRON MICROSCOPY	2.9
8F0R	ELECTRON MICROSCOPY	2.9
8I5X	ELECTRON MICROSCOPY	2.9
8S9B	ELECTRON MICROSCOPY	2.9
8THG	ELECTRON MICROSCOPY	2.9
9ITI	ELECTRON MICROSCOPY	2.92
21TP	ELECTRON MICROSCOPY	3
7W9M	ELECTRON MICROSCOPY	3
7W9T	ELECTRON MICROSCOPY	3
8J4F	ELECTRON MICROSCOPY	3
7XMF	ELECTRON MICROSCOPY	3.07
7XMG	ELECTRON MICROSCOPY	3.09
8F0S	ELECTRON MICROSCOPY	3.1
6J8G	ELECTRON MICROSCOPY	3.2
6J8H	ELECTRON MICROSCOPY	3.2
6J8I	ELECTRON MICROSCOPY	3.2
6J8J	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15858-F1	69.53	0.18

Antibody-complex structures (SAbDab): 3 — 6N4Q, 6N4R, 8YHZ

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 822 (is directly targeted by the spider protoxin-ii); 827 (is directly targeted by the spider protoxin-ii)

Post-translational modifications (1): 1490

Disulfide bonds (7): 275–324, 895, 895, 897–903, 935–944, 1350–1370, 1715–1730

Glycosylation sites (5): 209, 283, 1352, 1366, 1375

Mutagenesis-validated functional residues (21):

Position	Phenotype
406	hyperpolarizes the voltage dependence of activation by 10.6 mv and prolonges fast-inactivation duration when coexpressed
764	5-fold less blocked by the spider huwentoxin-iv.
778	5-fold less inhibited by the spider protoxin-ii.
822	no change in inhibition (ic(50)) by the spider protoxin-ii, but has a significant impact on channel activation by shifit
822	18-fold less blocked by the spider huwentoxin-iv.
823	9-fold less inhibited by the spider protoxin-ii.
824	4-fold less inhibited by the spider protoxin-ii.
824	less inhibited by the spider protoxin-ii.
825	no change in inhibition by the spider protoxin-ii.
825	19-fold less blocked by the spider huwentoxin-iv.
826	8-fold less inhibited by the spider protoxin-ii.
827	13-fold less blocked by the spider huwentoxin-iv, 3-fold less inhibited by the spider protoxin-ii, and has a significant
829	400-fold less blocked by the spider huwentoxin-iv.
1409–1410	important increase in inhibition by saxitoxin and little increase in inhibition by tetrodotoxin.
1490	abolishes stimulation by agents that stimulate pkc activity.
1490	increases current amplitude.
1597	decrease of the inhibition of fast inactivation produced by scorpion alpha-toxins cviv4 and aah2 on this channel.
1600	decrease of the inhibition of fast inactivation produced by the scorpion alpha-toxin cviv4 on this channel.
1643	depolarizes the voltage-dependence of steady-state fast inactivation; enhances persistent current.
1643	no effect on voltage-dependence of steady-state fast inactivation.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-445095	Interaction between L1 and Ankyrins
R-HSA-5576892	Phase 0 - rapid depolarisation
R-HSA-9717207	Sensory perception of sweet, bitter, and umami (glutamate) taste
R-HSA-1266738	Developmental Biology
R-HSA-373760	L1CAM interactions
R-HSA-397014	Muscle contraction
R-HSA-422475	Axon guidance
R-HSA-5576891	Cardiac conduction
R-HSA-9675108	Nervous system development
R-HSA-9709957	Sensory Perception
R-HSA-9717189	Sensory perception of taste

MSigDB gene sets: 522 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_DETECTION_OF_MECHANICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_MEMBRANE_DEPOLARIZATION_DURING_ACTION_POTENTIAL, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_DETECTION_OF_MECHANICAL_STIMULUS, GOBP_SENSORY_PERCEPTION_OF_PAIN, GOBP_DETECTION_OF_TEMPERATURE_STIMULUS

GO Biological Process (22): inflammatory response (GO:0006954), circadian rhythm (GO:0007623), response to toxic substance (GO:0009636), post-embryonic development (GO:0009791), neuronal action potential (GO:0019228), sensory perception of pain (GO:0019233), sodium ion transmembrane transport (GO:0035725), behavioral response to pain (GO:0048266), detection of temperature stimulus involved in sensory perception of pain (GO:0050965), detection of mechanical stimulus involved in sensory perception (GO:0050974), cardiac muscle cell action potential involved in contraction (GO:0086002), action potential propagation (GO:0098870), action potential (GO:0001508), regulation of heart rate (GO:0002027), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), monoatomic ion transmembrane transport (GO:0034220), regulation of membrane potential (GO:0042391), transmembrane transport (GO:0055085), cardiac muscle cell action potential (GO:0086001), regulation of muscle system process (GO:0090257), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (5): voltage-gated sodium channel activity (GO:0005248), monoatomic ion channel activity (GO:0005216), monoatomic cation channel activity (GO:0005261), sodium channel activity (GO:0005272), protein binding (GO:0005515)

GO Cellular Component (9): voltage-gated sodium channel complex (GO:0001518), plasma membrane (GO:0005886), axon (GO:0030424), node of Ranvier (GO:0033268), axon terminus (GO:0043679), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702), cell projection (GO:0042995), neuron projection (GO:0043005)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
L1CAM interactions	1
Cardiac conduction	1
Sensory perception of taste	1
Axon guidance	1
Nervous system development	1
Muscle contraction	1
Developmental Biology	1
Sensory Perception	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
action potential	3
cellular anatomical structure	3
sensory perception	2
regulation of biological quality	2
transport	2
defense response	1
rhythmic process	1
response to chemical	1
multicellular organism development	1
multicellular organismal process	1
transmission of nerve impulse	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
behavior	1
response to pain	1
sensory perception of pain	1
detection of temperature stimulus involved in sensory perception	1
detection of stimulus involved in sensory perception	1
sensory perception of mechanical stimulus	1
detection of mechanical stimulus	1
cardiac muscle cell action potential	1
cardiac muscle cell contraction	1
regulation of membrane potential	1
regulation of heart contraction	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
monoatomic ion transmembrane transport	1
cellular process	1
sodium channel activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic ion channel activity	1
monoatomic cation transmembrane transporter activity	1
monoatomic cation channel activity	1
sodium ion transmembrane transporter activity	1
binding	1
sodium channel complex	1
plasma membrane protein complex	1
membrane	1

Protein interactions and networks

STRING

1544 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCN9A	SCN1B	Q07699	935
SCN9A	GABRG2	P18507	861
SCN9A	NAV1	Q8NEY1	816
SCN9A	AGL	P35573	810
SCN9A	MPV17	P39210	810
SCN9A	SCN2B	O60939	802
SCN9A	TRPV1	Q8NER1	769
SCN9A	SCN4B	Q8IWT1	746
SCN9A	TRPA1	O75762	737
SCN9A	CRMP1	Q14194	706
SCN9A	CALM1	P02593	699
SCN9A	DPYSL2	Q16555	686
SCN9A	GABRD	O14764	654
SCN9A	ADGRV1	Q8WXG9	644
SCN9A	ASIC3	Q9UHC3	632

IntAct

16 interactions, top by confidence:

A	B	Type	Score
SMURF2	SCN9A	psi-mi:“MI:0407”(direct interaction)	0.440
SCN9A	G3BP2	psi-mi:“MI:0407”(direct interaction)	0.440
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
SCN2A	IGLL5	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SYT5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	CACNB4	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
SCN2A	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
CRELD1	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC44A1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): SCN9A (Synthetic Lethality), SCN9A (Proximity Label-MS), SCN9A (Affinity Capture-MS), SCN9A (Affinity Capture-MS), SCN9A (Proximity Label-MS), SCN9A (Affinity Capture-MS), SCN9A (Protein-peptide), SCN9A (Affinity Capture-MS), SCN9A (Cross-Linking-MS (XL-MS)), Dpysl2 (Protein-peptide), SCN9A (Cross-Linking-MS (XL-MS)), SCN9A (Affinity Capture-MS), SCN9A (Affinity Capture-MS), SCN9A (Affinity Capture-Western), SCN9A (Affinity Capture-MS)

ESM2 similar proteins: A2APX8, A2ASI5, B1AWN6, C9D7C2, D0E0C2, O08562, O35505, O46669, O73700, O88420, O88457, P02719, P04774, P04775, P08104, P0DMA5, P15381, P15389, P15390, P22002, P27732, P35498, P35499, P35500, Q01815, Q07652, Q13936, Q14524, Q15858, Q20JQ7, Q28371, Q28644, Q2XVR3, Q2XVR4, Q2XVR5, Q2XVR6, Q2XVR7, Q62205, Q62968, Q6QIY3

Diamond homologs: A2APX8, A2ASI5, B1AWN6, B1AYL1, D0E0C2, F1LQQ7, O00555, O08562, O46669, O73705, O73706, O73707, O88420, O88457, P02719, P04774, P04775, P08104, P0DMA5, P15389, P15390, P27884, P35498, P35499, P35500, P54282, P56699, P97445, Q01118, Q02789, Q05973, Q14524, Q15858, Q15878, Q20JQ7, Q28371, Q28644, Q2XVR3, Q2XVR4, Q2XVR5

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
SCN9A	“up-regulates quantity”	sodium(1+)	relocalization
FGF13	“down-regulates activity”	SCN9A	binding
FGF12	“down-regulates activity”	SCN9A	binding
FGF14	“down-regulates activity”	SCN9A	binding
FGF11	“down-regulates activity”	SCN9A	binding
SCN9A	up-regulates	Action_potential
FYN	“up-regulates activity”	SCN9A	phosphorylation
NEDD4L	“down-regulates quantity by destabilization”	SCN9A	ubiquitination
POU4F1	“up-regulates quantity by expression”	SCN9A	“transcriptional regulation”
AR	“up-regulates quantity by expression”	SCN9A	“transcriptional regulation”
ESR1	“down-regulates quantity by repression”	SCN9A	“transcriptional regulation”
ESR2	“down-regulates quantity by repression”	SCN9A	“transcriptional regulation”
TNF	“up-regulates quantity by expression”	SCN9A	“transcriptional regulation”
TNF	“up-regulates activity”	SCN9A
NGF	“up-regulates quantity by expression”	SCN9A	“transcriptional regulation”
IL10	“down-regulates quantity by repression”	SCN9A	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

1619 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	68
Likely pathogenic	33
Uncertain significance	962
Likely benign	424
Benign	36

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1024965	NM_001365536.1(SCN9A):c.2599G>C (p.Gly867Arg)	Pathogenic
1065200	NM_001365536.1(SCN9A):c.4048T>C (p.Cys1350Arg)	Pathogenic
1068637	NM_001365536.1(SCN9A):c.5100G>A (p.Trp1700Ter)	Pathogenic
1070653	NM_001365536.1(SCN9A):c.2984_2985insC (p.Ile995_Lys996insTer)	Pathogenic
1070796	NM_001365536.1(SCN9A):c.4740_4743dup (p.Asp1582delinsPheTer)	Pathogenic
1074563	NC_000002.11:g.(?167055172)(167060984_?)del	Pathogenic
1075008	NM_001365536.1(SCN9A):c.116del (p.Lys39fs)	Pathogenic
1075796	NM_001365536.1(SCN9A):c.2667dup (p.Lys890Ter)	Pathogenic
1076717	NM_001365536.1(SCN9A):c.2409T>A (p.Tyr803Ter)	Pathogenic
1076959	NM_001365536.1(SCN9A):c.3801+1G>A	Pathogenic
1174115	NM_001365536.1(SCN9A):c.377+7T>G	Pathogenic
1355824	NM_001365536.1(SCN9A):c.3183_3199del (p.Phe1062fs)	Pathogenic
1378654	NM_001365536.1(SCN9A):c.4195_4196del (p.Leu1399fs)	Pathogenic
1448916	NM_001365536.1(SCN9A):c.4828C>T (p.Arg1610Ter)	Pathogenic
1451242	NM_001365536.1(SCN9A):c.3352-1G>A	Pathogenic
1702989	NM_001365536.1(SCN9A):c.596+1G>A	Pathogenic
1991866	NM_001365536.1(SCN9A):c.3550del (p.Thr1184fs)	Pathogenic
2014121	NM_001365536.1(SCN9A):c.500C>A (p.Ser167Ter)	Pathogenic
2056928	NM_001365536.1(SCN9A):c.381dup (p.Phe128fs)	Pathogenic
2064727	NM_001365536.1(SCN9A):c.2064_2065del (p.Arg688fs)	Pathogenic
2108660	NM_001365536.1(SCN9A):c.1635del (p.Ala546fs)	Pathogenic
2148736	NM_001365536.1(SCN9A):c.1528del (p.Arg510fs)	Pathogenic
2423908	NC_000002.11:g.(?166895913)(167145173_?)del	Pathogenic
2424581	NC_000002.11:g.(?167055182)(167056394_?)del	Pathogenic
2424582	NC_000002.11:g.(?167083057)(167099186_?)del	Pathogenic
2424583	NC_000002.11:g.(?167085181)(167168266_?)del	Pathogenic
2424588	NC_000002.11:g.(?166847749)(167060980_?)del	Pathogenic
245799	NM_001365536.1(SCN9A):c.4495C>T (p.Arg1499Ter)	Pathogenic
245903	NM_001365536.1(SCN9A):c.4928C>A (p.Ala1643Glu)	Pathogenic
2925329	NM_001365536.1(SCN9A):c.2941G>T (p.Glu981Ter)	Pathogenic

SpliceAI

5035 predictions. Top by Δscore:

Variant	Effect	Δscore
2:166204358:ACC:A	donor_gain	1.0000
2:166204359:CCC:C	donor_gain	1.0000
2:166204461:CAAGG:C	acceptor_gain	1.0000
2:166204462:A:T	acceptor_gain	1.0000
2:166204465:G:GC	acceptor_gain	1.0000
2:166226565:A:AC	donor_gain	1.0000
2:166226565:ATCTT:A	donor_gain	1.0000
2:166226635:C:T	acceptor_gain	1.0000
2:166228689:A:AC	donor_gain	1.0000
2:166228690:C:CC	donor_gain	1.0000
2:166228690:CAA:C	donor_gain	1.0000
2:166228881:C:CA	donor_gain	1.0000
2:166228969:CGAC:C	acceptor_gain	1.0000
2:166238092:A:AC	donor_gain	1.0000
2:166238093:C:CC	donor_gain	1.0000
2:166238093:CAT:C	donor_gain	1.0000
2:166238264:AAGCC:A	acceptor_loss	1.0000
2:166238266:GCC:G	acceptor_loss	1.0000
2:166238267:CCT:C	acceptor_loss	1.0000
2:166238268:CTGTG:C	acceptor_loss	1.0000
2:166238269:T:A	acceptor_loss	1.0000
2:166277335:CGGAG:C	acceptor_gain	1.0000
2:166277340:C:CC	acceptor_gain	1.0000
2:166278139:CCAGT:C	donor_gain	1.0000
2:166278240:A:AC	donor_gain	1.0000
2:166278241:C:CC	donor_gain	1.0000
2:166278313:CCTA:C	acceptor_loss	1.0000
2:166278314:C:T	acceptor_loss	1.0000
2:166280596:C:CC	acceptor_gain	1.0000
2:166284452:CG:C	donor_gain	1.0000

AlphaMissense

13297 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:166199283:A:G	W1786R	1.000
2:166199283:A:T	W1786R	1.000
2:166199380:G:C	N1753K	1.000
2:166199380:G:T	N1753K	1.000
2:166199539:C:A	W1700C	1.000
2:166199539:C:G	W1700C	1.000
2:166199541:A:G	W1700R	1.000
2:166199541:A:T	W1700R	1.000
2:166226604:C:T	G1454D	1.000
2:166226605:C:G	G1454R	1.000
2:166226613:A:C	L1451W	1.000
2:166226613:A:G	L1451S	1.000
2:166227708:A:G	W1408R	1.000
2:166227708:A:T	W1408R	1.000
2:166228903:A:G	W1332R	1.000
2:166228903:A:T	W1332R	1.000
2:166228915:A:G	C1328R	1.000
2:166233374:G:C	P1297R	1.000
2:166238123:A:G	W1258R	1.000
2:166238123:A:T	W1258R	1.000
2:166242511:A:C	S1206R	1.000
2:166242511:A:T	S1206R	1.000
2:166242513:T:G	S1206R	1.000
2:166272865:A:G	L962P	1.000
2:166277025:G:C	C944W	1.000
2:166277027:A:G	C944R	1.000
2:166277052:A:C	C935W	1.000
2:166277058:C:A	W933C	1.000
2:166277058:C:G	W933C	1.000
2:166277073:C:A	W928C	1.000

dbSNP variants (sampled 300 via entrez): RS1000023423 (2:166362530 A>G), RS1000029298 (2:166355537 G>A), RS1000045575 (2:166207421 G>T), RS1000052686 (2:166306146 A>C), RS1000082266 (2:166225645 A>C), RS1000085439 (2:166351101 T>A,C), RS1000091174 (2:166295821 C>T), RS1000104010 (2:166270695 G>A), RS1000117119 (2:166305427 G>A), RS1000122255 (2:166304775 T>C), RS1000128305 (2:166277179 T>C), RS1000133599 (2:166232389 T>C), RS1000136521 (2:166350875 A>C), RS1000196986 (2:166213072 G>C), RS1000212450 (2:166218148 G>C)

Disease associations

OMIM: gene MIM:603415 | disease phenotypes: MIM:613863, MIM:201300, MIM:133020, MIM:167400, MIM:243000, MIM:604233, MIM:606482, MIM:117100

GenCC curated gene-disease

Disease	Classification	Inheritance
primary erythermalgia	Definitive	Autosomal dominant
channelopathy-associated congenital insensitivity to pain, autosomal recessive	Strong	Autosomal recessive
generalized epilepsy with febrile seizures plus, type 7	Strong	Autosomal dominant
paroxysmal extreme pain disorder	Strong	Autosomal dominant
hereditary peripheral neuropathy	Strong	Semidominant
sodium channelopathy-related small fiber neuropathy	Supportive	Autosomal dominant
hereditary sensory and autonomic neuropathy type 2	Supportive	Autosomal recessive
epilepsy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
epilepsy	Refuted	AD

Mondo (17): generalized epilepsy with febrile seizures plus, type 7 (MONDO:0013470), neuropathy, hereditary sensory and autonomic, type 2A (MONDO:0024309), primary erythermalgia (MONDO:0007571), paroxysmal extreme pain disorder (MONDO:0008179), channelopathy-associated congenital insensitivity to pain, autosomal recessive (MONDO:0009459), Dravet syndrome (MONDO:0100135), generalized epilepsy with febrile seizures plus (MONDO:0018214), developmental and epileptic encephalopathy (MONDO:0100620), neuropathy, small fiber (MONDO:0800207), Charcot-Marie-Tooth disease dominant intermediate B (MONDO:0011674), self-limited epilepsy with centrotemporal spikes (MONDO:0007295), febrile seizures, familial, 3b (MONDO:0800354), epilepsy (MONDO:0005027), autism spectrum disorder (MONDO:0005258), (MONDO:0017629)

Orphanet (11): Genetic epilepsy with febrile seizure plus (Orphanet:36387), Hereditary sensory and autonomic neuropathy type 2 (Orphanet:970), Hereditary sodium channelopathy-related small fibers neuropathy (Orphanet:306577), Paroxysmal extreme pain disorder (Orphanet:46348), Congenital insensitivity to pain-anosmia-neuropathic arthropathy (Orphanet:88642), Primary erythromelalgia (Orphanet:90026), Dravet syndrome (Orphanet:33069), Autosomal dominant intermediate Charcot-Marie-Tooth disease type B (Orphanet:100044), Autosomal dominant Charcot-Marie-Tooth disease type 2M (Orphanet:228179), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

144 total (30 of 144 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000217	Xerostomia
HP:0000224	Hypogeusia
HP:0000458	Anosmia
HP:0000466	Limited neck range of motion
HP:0000622	Blurred vision
HP:0000632	Lacrimation abnormality
HP:0000729	Autistic behavior
HP:0000736	Short attention span
HP:0000739	Anxiety
HP:0000762	Decreased nerve conduction velocity
HP:0000966	Hypohidrosis
HP:0000970	Anhidrosis
HP:0000975	Hyperhidrosis
HP:0000980	Pallor
HP:0000989	Pruritus
HP:0001069	Episodic hyperhidrosis
HP:0001097	Keratoconjunctivitis sicca
HP:0001182	Tapered finger
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001300	Parkinsonism
HP:0001327	Photosensitive myoclonic seizure

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001786_11	Dental caries	7.000000e-06
GCST003465_13	Cannabis dependence symptom count	2.000000e-07
GCST008361_7	Response to cognitive-behavioural therapy in major depressive disorder	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008457	cannabis dependence measurement
EFO:0007820	cognitive behavioural therapy

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
C567827	Generalized Epilepsy With Febrile Seizures Plus, 7 (supp.)
C565808	Generalized Epilepsy with Febrile Seizures Plus (supp.)
C563475	Paroxysmal Extreme Pain Disorder (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2331043 (PROTEIN FAMILY), CHEMBL4296 (SINGLE PROTEIN), CHEMBL4523670 (PROTEIN COMPLEX), CHEMBL4630765 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

36 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 740,735 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL12713	SERTINDOLE	4	8,984
CHEMBL1423	PIMOZIDE	4	17,310
CHEMBL193	NIFEDIPINE	4	74,353
CHEMBL23	DILTIAZEM	4	54,676
CHEMBL45816	MIBEFRADIL	4	7,838
CHEMBL54	HALOPERIDOL	4	60,883
CHEMBL558	MEXILETINE	4	15,463
CHEMBL629	AMITRIPTYLINE	4	52,595
CHEMBL633	AMIODARONE	4	29,704
CHEMBL71	CHLORPROMAZINE	4	45,827
CHEMBL108	CARBAMAZEPINE	4	53,528
CHEMBL1200606	MEXILETINE HYDROCHLORIDE	4	4,087
CHEMBL190461	CANNABIDIOL	4	26,379
CHEMBL396778	SAFINAMIDE	4	1,454
CHEMBL58323	LACOSAMIDE	4	5,692
CHEMBL698	TETRACAINE	4	43,379
CHEMBL741	LAMOTRIGINE	4	28,962
CHEMBL744	RILUZOLE	4	20,055
CHEMBL79	LIDOCAINE	4	140,673
CHEMBL113461	TEDISAMIL	3
CHEMBL475534	NITRENDIPINE	3
CHEMBL5314404	AJMALINE	3
CHEMBL2107771	RALFINAMIDE	3
CHEMBL3544913	VIXOTRIGINE	3
CHEMBL3707392	ELECLAZINE	3
CHEMBL507974	TETRODOTOXIN	3
CHEMBL87045	CIFENLINE	2
CHEMBL2325014	PF-05089771	2
CHEMBL3589904	PF-04531083	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12478318	SCN9A		0.00	0
rs6746030	SCN9A		0.00	0
rs41268673	SCN9A		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — Voltage-gated sodium channels (Na_V)

Most potent curated ligand interactions (23 total), top 23:

Ligand	Action	Affinity	Parameter
PF‐06526290	Inhibition	9.57	pEC50
AM-6120	Inhibition	9.1	pIC50
GNE-616	Inhibition	9.1	pKi
XEN907	Inhibition	8.5	pIC50
GNE-131	Binding	8.0	pIC50
PF-05089771	Channel blocker	7.96	pIC50
DS-1971a	Inhibition	7.61	pIC50
tetrodotoxin	Pore blocker	7.6	pIC50
PF-04856264	Channel blocker	7.55	pIC50
funapide	Inhibition	7.27	pIC50
N-Me-aminopyrimidinone 9	Inhibition	7.1	pIC50
pyrrolopyrimidine 48 [PMID: 22318156]	Inhibition	7.0	pIC50
cannabidiol	Channel blocker	6.7	pIC50
saxitoxin	Pore blocker	6.2	pIC50
ABBV-318	Inhibition	5.55	pIC50
vixotrigine	Inhibition	5.21	pIC50
ANP-230	Channel blocker	5.15	pIC50
cannabigerol	Channel blocker	4.73	pIC50
cannabinol	Channel blocker	4.52	pIC50
amorolfine	Channel blocker	4.02	pIC50
lacosamide	Antagonist	3.7	pIC50
lidocaine	Pore blocker	3.3	pIC50
Cd2+	Pore blocker	3.0	pIC50

Binding affinities (BindingDB)

4957 measured of 6100 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[4-chloro-2-[3-(dimethylamino)-1,2-benzoxazol-5-yl]phenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	0.2 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
(R)-N-(6-Fluoropyridin-2-yl)-4-(2-(2-methyloxazol-4-yl)-4-(trifluoromethyl)phenyl)chroman-7-sulfonamide	IC50	0.2 nM	US-10239869: Sulfonamide compounds as voltage-gated sodium channel modulators
4-[4-chloro-2-(2-oxo-3H-1,3-benzoxazol-5-yl)phenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	0.3 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
N-(azetidin-1-ylsulfonyl)-5-cyclopropyl-4-[(3,5-dichlorophenoxy)methyl]-2-fluorobenzamide	IC50	0.3 nM	US-10071957: N-substituted benzamides and methods of use thereof
(R)-N-(6-Fluoropyridin-2-yl)-4-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)chroman-7-sulfonamide	IC50	0.3 nM	US-10239869: Sulfonamide compounds as voltage-gated sodium channel modulators
4-[2-(2-amino-3H-benzimidazol-5-yl)-4-chlorophenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	0.3 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
5-cyclopropyl-4-[(3R)-1-[(3,5-dichlorophenyl)methyl]piperidin-3-yl]oxy-2-fluoro-N-methylsulfonylbenzamide	IC50	0.3 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[2-(3-amino-1,2-benzoxazol-5-yl)-4-chlorophenoxy]-2,6-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	0.5 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
4-[4-chloro-2-[3-(methylamino)-1,2-benzoxazol-5-yl]phenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	0.5 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
4-[2-(3-amino-1,2-benzoxazol-5-yl)-4-chlorophenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	0.6 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
2,5-difluoro-4-[4-methyl-2-(2-oxo-3H-1,3-benzoxazol-5-yl)phenoxy]-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	0.7 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
4-(2-(3-fluoropropyl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)chroman-7-sulfonamide	IC50	0.7 nM	US-10239869: Sulfonamide compounds as voltage-gated sodium channel modulators
2,6-difluoro-4-[(3R)-3-[methyl-[(3R)-oxolan-3-yl]amino]-3-[2-[3-(trifluoromethyl)phenyl]ethyl]piperidin-1-yl]-N-pyrimidin-4-ylbenzenesulfonamide	IC50	0.7 nM	US-20240239766: 3-AMINO PIPERIDYL SODIUM CHANNEL INHIBITORS
4-[2-(2-amino-1,3-benzoxazol-6-yl)-4-chlorophenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	0.8 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
5-cyclopropyl-N-cyclopropylsulfonyl-4-[[1-[(3,5-dichlorophenyl)-phenylmethyl]piperidin-4-yl]methoxy]-2-fluorobenzamide	IC50	0.8 nM	US-9694002: Substituted benzamides and methods of use thereof
(4R)-4-[2-(2-methyl-1,3-thiazol-4-yl)-4-(trifluoromethyl)phenyl]-N-pyrimidin-4-yl-3,4-dihydro-2H-chromene-7-sulfonamide	IC50	0.9 nM	US-10239869: Sulfonamide compounds as voltage-gated sodium channel modulators
(S)-N-(6-fluoropyridin-2-yl)-4-(2-(((S)-tetrahydrofuran-3-yl)oxy)-4-(trifluoromethyl)phenyl)chroman-7-sulfonamide	IC50	0.9 nM	US-10239869: Sulfonamide compounds as voltage-gated sodium channel modulators
4-[(3R)-3-[2-[4-chloro-3-(trifluoromethyl)phenyl]ethyl]-3-(dimethylamino)piperidin-1-yl]-2,6-difluoro-N-pyrimidin-4-ylbenzenesulfonamide	IC50	0.9 nM	US-20240239766: 3-AMINO PIPERIDYL SODIUM CHANNEL INHIBITORS
6-(((1S,2S,4S)-2-(dimethyl- amino)-4-(4-fluoro-3- (trifluoromethyl)phenyl)- cyclohexyl)oxy)-2-methyl-N- (pyrimidin-4-yl)pyridine-3- sulfonamide formate	IC50	0.913 nM	US-20250115576: THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF
4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	1 nM	US-8952169: N-substituted benzamides and methods of use thereof
4-(1-adamantylmethoxy)-5-cyclopropyl-N-cyclopropylsulfonyl-2-fluorobenzamide	IC50	1 nM	US-8952169: N-substituted benzamides and methods of use thereof
4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-(3-fluoroazetidin-1-yl)sulfonylbenzamide	IC50	1 nM	US-8952169: N-substituted benzamides and methods of use thereof
5-cyclopropyl-4-[(4,4-difluoro-1-adamantyl)methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	1 nM	US-8952169: N-substituted benzamides and methods of use thereof
4-(1-adamantylmethoxy)-5-cyclopropyl-N-ethylsulfonyl-2-fluorobenzamide	IC50	1 nM	US-8952169: N-substituted benzamides and methods of use thereof
4-(2-adamantylmethoxy)-N-(azetidin-1-ylsulfonyl)-5-cyclopropyl-2-fluorobenzamide	IC50	1 nM	US-8952169: N-substituted benzamides and methods of use thereof
4-[2-(1,3-benzoxazol-5-yl)-4-chlorophenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	1 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
4-[4-chloro-2-(2-oxo-1,3-dihydroindol-6-yl)phenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	1 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
(R)-N-(4-Fluoropyridin-2-yl)-4-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)chroman-7-sulfonamide	IC50	1 nM	US-10239869: Sulfonamide compounds as voltage-gated sodium channel modulators
(R)-4-(2-(5-fluoropyridin-2-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)chroman-7-sulfonamide	IC50	1 nM	US-10239869: Sulfonamide compounds as voltage-gated sodium channel modulators
6-(((1S,2S,4S)-4-(3,5- dichlorophenyl)-2-(dimethyl- amino)cyclohexyl)oxy)-2- methyl-N-(pyrimidin-4- yl)pyridine-3-sulfonamide	IC50	1.12 nM	US-20250115576: THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF
4-[2-(2-amino-3H-benzimidazol-5-yl)-4-chlorophenoxy]-2,6-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	1.2 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
4-[(3R)-1-[[3-chloro-5-(trifluoromethoxy)phenyl]methyl]piperidin-3-yl]oxy-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	1.3 nM	US-9694002: Substituted benzamides and methods of use thereof
6-(((1S,2S,4S)-2-(dimethyl- amino)-4-(4-methyl-3- (trifluoromethyl)phenyl)- cyclohexyl)oxy)-2-methyl-N- (pyrimidin-4-yl)pyridine-3- sulfonamide formate	IC50	1.32 nM	US-20250115576: THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF
6-(((1S,2S,4S)-4-(3,4-dichloro- phenyl)-2-(dimethylamino)- cyclohexyl)oxy)-2-methyl-N- (pyrimidin-4-yl)pyridine-3- sulfonamide	IC50	1.36 nM	US-20250115576: THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF
4-[4-chloro-2-[2-(trifluoromethyl)-3H-benzimidazol-5-yl]phenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	1.4 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
4-[2-(2-amino-1,3-benzoxazol-5-yl)-4-chlorophenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	1.4 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
5-cyclopropyl-4-[[1-[(3,5-dichlorophenyl)-phenylmethyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	1.5 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(2S)-2-(3,5-dichlorophenyl)-1-methoxypropan-2-yl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	1.6 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(1S)-1-(3,5-dichlorophenyl)-2-methoxy-2-methylpropyl]piperidin-4-yl]methoxy]-N-ethylsulfonyl-2-fluorobenzamide	IC50	1.6 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(1S)-1-(3,5-dichloro-2-fluorophenyl)ethyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	1.6 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[[1-[1-(2-chloro-4-fluorophenyl)-2,2,2-trifluoroethyl]piperidin-4-yl]methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	1.6 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[2-(3H-benzimidazol-5-yl)-4-chlorophenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	1.7 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
4-[4-chloro-2-(2-oxo-1,3-dihydrobenzimidazol-5-yl)phenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	1.7 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
4-[2-(3-amino-1,2-benzoxazol-5-yl)-4-fluorophenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	IC50	1.7 nM	US-9481677: Biaryl ether sulfonamides and their use as therapeutic agents
2,6-difluoro-4-[(3R)-3-[methyl-[(3S)-oxolan-3-yl]amino]-3-[2-[3-(trifluoromethyl)phenyl]ethyl]piperidin-1-yl]-N-pyrimidin-4-ylbenzenesulfonamide	IC50	1.7 nM	US-20240239766: 3-AMINO PIPERIDYL SODIUM CHANNEL INHIBITORS
4-[(3R)-1-[(2-chlorophenyl)methyl]piperidin-3-yl]oxy-5-cyclopropyl-N-cyclopropylsulfonyl-2-fluorobenzamide	IC50	1.7 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[(3R)-1-[(2,4-dichlorophenyl)methyl]piperidin-3-yl]oxy-2-fluoro-N-methylsulfonylbenzamide	IC50	1.7 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(1R)-1-(3,5-dichlorophenyl)-2-methoxy-2-methylpropyl]piperidin-4-yl]methoxy]-N-ethylsulfonyl-2-fluorobenzamide	IC50	1.7 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[2-(3,5-dichlorophenyl)propan-2-yl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	1.7 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(1S)-1-(3,5-dichlorophenyl)ethyl]-4-methylpiperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	1.7 nM	US-9694002: Substituted benzamides and methods of use thereof

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL4217988
10.74	Ki	0.018	nM	CHEMBL1224266
10.52	IC50	0.03	nM	CHEMBL4217988
10.38	IC50	0.042	nM	CHEMBL3318148
10.00	IC50	0.1	nM	CHEMBL4210135
10.00	IC50	0.1	nM	CHEMBL4205773
9.96	IC50	0.11	nM	CHEMBL4640389
9.96	Ki	0.111	nM	CHEMBL1224265
9.92	IC50	0.12	nM	CHEMBL4215058
9.85	IC50	0.141	nM	CHEMBL5994244
9.76	IC50	0.173	nM	CHEMBL5819252
9.74	IC50	0.182	nM	CHEMBL5758486
9.70	IC50	0.2	nM	CHEMBL3318134
9.70	IC50	0.2	nM	CHEMBL3955386
9.70	IC50	0.2	nM	CHEMBL4162835
9.70	IC50	0.2	nM	CHEMBL4163942
9.70	IC50	0.2	nM	CHEMBL5962168
9.64	IC50	0.23	nM	CHEMBL3318147
9.62	IC50	0.241	nM	CHEMBL5970328
9.59	IC50	0.26	nM	CHEMBL4169884
9.58	IC50	0.263	nM	CHEMBL5842524
9.52	IC50	0.3	nM	CHEMBL3657851
9.52	IC50	0.3	nM	CHEMBL3617063
9.52	IC50	0.3	nM	CHEMBL3965272
9.52	IC50	0.3	nM	CHEMBL4173743
9.52	IC50	0.3	nM	CHEMBL4159473
9.52	IC50	0.3	nM	CHEMBL4224739
9.52	IC50	0.3	nM	CHEMBL3318132
9.52	IC50	0.3	nM	CHEMBL6033883
9.52	IC50	0.305	nM	CHEMBL6023013
9.50	IC50	0.317	nM	CHEMBL5994244
9.49	Ki	0.32	nM	CHEMBL4462278
9.49	IC50	0.322	nM	CHEMBL5804418
9.49	IC50	0.325	nM	CHEMBL5956152
9.48	IC50	0.327	nM	CHEMBL5745233
9.48	IC50	0.334	nM	CHEMBL5845658
9.45	IC50	0.355	nM	CHEMBL5822832
9.43	IC50	0.372	nM	CHEMBL6065878
9.42	Kd	0.38	nM	CHEMBL4464990
9.42	IC50	0.383	nM	CHEMBL6050898
9.40	IC50	0.4	nM	CHEMBL3657855
9.40	IC50	0.4	nM	CHEMBL3341983
9.40	IC50	0.4	nM	CHEMBL4646742
9.40	IC50	0.4	nM	CHEMBL4634421
9.38	IC50	0.418	nM	CHEMBL5748503
9.34	IC50	0.462	nM	CHEMBL5923998
9.31	IC50	0.494	nM	CHEMBL5749061
9.30	IC50	0.5	nM	CHEMBL3806065
9.30	IC50	0.5	nM	CHEMBL3957974
9.30	IC50	0.5	nM	CHEMBL4174312

PubChem BioAssay actives

3275 with measured affinity, of 4197 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[3-(2-chlorophenyl)phenyl]pyrazole-1-carboxamide	502582: Inhibition of human Nav 1.7 channel by electrophysiology	ki	<0.0001	uM
3-cyano-4-[2-[2-[(2-piperidin-4-ylethylamino)methyl]-4-pyridinyl]-4-[3-(trifluoromethyl)phenyl]phenoxy]-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1365863: Inhibition of human Nav1.7 expressed in HEK cells by patch clamp electrophysiology method	ic50	<0.0001	uM
3-[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-65-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]carbamoyl]-27,57-bis(4-aminobutyl)-21-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-24-(3-amino-3-oxopropyl)-54,74-bis(3-carbamimidamidopropyl)-51-(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36,68-tris(1H-indol-3-ylmethyl)-71-(2-methylpropyl)-7,33-bis(2-methylsulfanylethyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-4-propan-2-yl-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontan-13-yl]propanoic acid	1183788: Inhibition of human Nav1.7 expressed in HEK-293 cells at -130 to -110 mV holding potential by whole-cell voltage clamp analysis	ic50	<0.0001	uM
4-[2-[2-(aminomethyl)-4-pyridinyl]-4-[3-(trifluoromethyl)phenyl]phenoxy]-3-cyano-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1365863: Inhibition of human Nav1.7 expressed in HEK cells by patch clamp electrophysiology method	ic50	0.0001	uM
(4R)-4-[2-(6-fluoro-3-pyridinyl)-4-(trifluoromethyl)phenyl]-N-pyrimidin-4-yl-3,4-dihydro-2H-chromene-7-sulfonamide	1668674: Inhibition of Nav1.7 (unknown origin) expressed in HEK293 cells assessed as reduction in veratridine-induced depolarization preincubated for 15 to 20 mins followed by veratridine stimulation by 1X red membrane potential dye based FLIPR assay	ic50	0.0001	uM
4-[2-[2-[[2-[1-[3-[4-(4-but-3-ynoxybenzoyl)phenyl]propanoyl]piperidin-4-yl]ethylamino]methyl]-4-pyridinyl]-4-[3-(trifluoromethyl)phenyl]phenoxy]-3-cyano-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1365863: Inhibition of human Nav1.7 expressed in HEK cells by patch clamp electrophysiology method	ic50	0.0001	uM
N-[2-[2-[3-[4-[2-[[4-[2-[2-cyano-4-(1,2,4-thiadiazol-5-ylsulfamoyl)phenoxy]-5-[3-(trifluoromethyl)phenyl]phenyl]-2-pyridinyl]methylamino]ethyl]piperidin-1-yl]-3-oxopropoxy]ethoxy]ethyl]-5-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)pentanamide	1365863: Inhibition of human Nav1.7 expressed in HEK cells by patch clamp electrophysiology method	ic50	0.0001	uM
3-[4-(2-chlorophenyl)phenyl]pyrazole-1-carboxamide	502582: Inhibition of human Nav 1.7 channel by electrophysiology	ki	0.0001	uM
(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-27,57-bis(4-aminobutyl)-21-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-24-(3-amino-3-oxopropyl)-54,74-bis(3-carbamimidamidopropyl)-13-(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36,68-tris(1H-indol-3-ylmethyl)-51-methyl-71-(2-methylpropyl)-7,33-bis(2-methylsulfanylethyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-4-propan-2-yl-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontane-65-carbonyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1183788: Inhibition of human Nav1.7 expressed in HEK-293 cells at -130 to -110 mV holding potential by whole-cell voltage clamp analysis	ic50	0.0002	uM
3-[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-65-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]carbamoyl]-27,57-bis(4-aminobutyl)-21-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-24-(3-amino-3-oxopropyl)-54,74-bis(3-carbamimidamidopropyl)-51-(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36,68-tris(1H-indol-3-ylmethyl)-71-(2-methylpropyl)-7,33-bis(2-methylsulfanylethyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-4-propan-2-yl-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontan-13-yl]propanoic acid	1183788: Inhibition of human Nav1.7 expressed in HEK-293 cells at -130 to -110 mV holding potential by whole-cell voltage clamp analysis	ic50	0.0002	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-27,51,74-tris(4-aminobutyl)-24-(3-amino-3-oxopropyl)-21-[[(2S)-2-[[(2S)-2-aminopent-4-ynoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-33-butyl-4,54-bis(3-carbamimidamidopropyl)-13-(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36,68-tris(1H-indol-3-ylmethyl)-57-methyl-7,71-bis(2-methylpropyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontane-65-carbonyl]amino]pentanoyl]amino]hexanoyl]amino]-5-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1363503: Inhibition of human Nav1.7 expressed in HEK293 cells at holding potential of -125 mV after 10 mins by patchxpress-based electrophysiology assay	ic50	0.0002	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-27,51,74-tris(4-aminobutyl)-24-(3-amino-3-oxopropyl)-21-[[(2S)-2-[[(2S)-2-aminopent-4-ynoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-33-butyl-4,54-bis(3-carbamimidamidopropyl)-13-(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36,68-tris(1H-indol-3-ylmethyl)-57-methyl-7,71-bis(2-methylpropyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontane-65-carbonyl]amino]pentanoyl]amino]hexanoyl]amino]-5-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-oxopentanoic acid	1363503: Inhibition of human Nav1.7 expressed in HEK293 cells at holding potential of -125 mV after 10 mins by patchxpress-based electrophysiology assay	ic50	0.0002	uM
(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-27,57-bis(4-aminobutyl)-21-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-24-(3-amino-3-oxopropyl)-54,74-bis(3-carbamimidamidopropyl)-13,51-bis(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36,68-tris(1H-indol-3-ylmethyl)-71-(2-methylpropyl)-7,33-bis(2-methylsulfanylethyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-4-propan-2-yl-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontane-65-carbonyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1388446: Inhibition of human Nav1.7 expressed in xenopus oocytes at -80 mV holding potential by two-electrode voltage-clamp method	ic50	0.0003	uM
(4S)-4-amino-5-[[(2S)-1-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-65-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]-27,51,74-tris(4-aminobutyl)-24-(3-amino-3-oxopropyl)-68-[(5-bromo-1H-indol-3-yl)methyl]-33-butyl-4,54-bis(3-carbamimidamidopropyl)-13-(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36-bis(1H-indol-3-ylmethyl)-57-methyl-7,71-bis(2-methylpropyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontan-21-yl]amino]-1-oxopent-4-yn-2-yl]amino]-5-oxopentanoic acid	1363503: Inhibition of human Nav1.7 expressed in HEK293 cells at holding potential of -125 mV after 10 mins by patchxpress-based electrophysiology assay	ic50	0.0003	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-27,51,74-tris(4-aminobutyl)-24-(3-amino-3-oxopropyl)-21-[[(2S)-2-[[(2S)-2-aminopent-4-ynoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-68-[(5-bromo-1H-indol-3-yl)methyl]-33-butyl-4,54-bis(3-carbamimidamidopropyl)-13-(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36-bis(1H-indol-3-ylmethyl)-57-methyl-7,71-bis(2-methylpropyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontane-65-carbonyl]amino]pentanoyl]amino]hexanoyl]amino]-5-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	1363503: Inhibition of human Nav1.7 expressed in HEK293 cells at holding potential of -125 mV after 10 mins by patchxpress-based electrophysiology assay	ic50	0.0003	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-27,51,74-tris(4-aminobutyl)-24-(3-amino-3-oxopropyl)-21-[[(2S)-2-[[(2S)-2-aminopent-4-ynoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-33-butyl-4,54-bis(3-carbamimidamidopropyl)-13-(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36,68-tris(1H-indol-3-ylmethyl)-57-methyl-7,71-bis(2-methylpropyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontane-65-carbonyl]amino]pentanoyl]amino]hexanoyl]amino]-5-[[(2S)-1-amino-1-oxo-4-phenylbutan-2-yl]amino]-5-oxopentanoic acid	1363503: Inhibition of human Nav1.7 expressed in HEK293 cells at holding potential of -125 mV after 10 mins by patchxpress-based electrophysiology assay	ic50	0.0003	uM
(4S)-6-fluoro-4-[(2R,4S)-2-(1H-pyrazol-5-yl)-4-(trifluoromethyl)piperidin-1-yl]-N-pyrimidin-4-yl-3,4-dihydro-2H-chromene-7-sulfonamide	1587784: Displacement of [3H]GX-545 from full length human Nav1.7 VSD4 domain expressed in HEK cell membranes measured after 20 hrs by liquid scintillation counting method	ki	0.0003	uM
4-[2-(2-amino-3H-benzimidazol-5-yl)-4-chlorophenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1300000: Inhibition of full length human Nav1.7 channel expressed in HEK cells co-expressing human sodium channel subunit beta1 at holding potential -60 mV by automated voltage clamp analysis	ic50	0.0003	uM
4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	1960118: Inhibition of human Nav1.7 alpha subunit expressed in HEK293 cells co-expressing beta1 subunit at -60 mV holding potential by whole-cell patch voltage clamp electrophysiology recording	ic50	0.0003	uM
(4S)-6-fluoro-4-[(2R,4S)-2-pyridin-2-yl-4-(trifluoromethyl)piperidin-1-yl]-N-pyrimidin-4-yl-3,4-dihydro-2H-chromene-7-sulfonamide	1587751: Inhibition of full length human Nav1.7 expressed in HEK293 cells at -60 mV holding potential by manual patch clamp electrophysiology method	kd	0.0004	uM
(4R)-4-[2-(6-fluoro-3-pyridinyl)-4-(trifluoromethyl)phenyl]-N-(1,3-thiazol-2-yl)-3,4-dihydro-2H-chromene-7-sulfonamide	1668674: Inhibition of Nav1.7 (unknown origin) expressed in HEK293 cells assessed as reduction in veratridine-induced depolarization preincubated for 15 to 20 mins followed by veratridine stimulation by 1X red membrane potential dye based FLIPR assay	ic50	0.0004	uM
(4R)-4-[2-(2-methylpyrazol-3-yl)-4-(trifluoromethyl)phenyl]-N-(1,3-thiazol-2-yl)-3,4-dihydro-2H-chromene-7-sulfonamide	1668674: Inhibition of Nav1.7 (unknown origin) expressed in HEK293 cells assessed as reduction in veratridine-induced depolarization preincubated for 15 to 20 mins followed by veratridine stimulation by 1X red membrane potential dye based FLIPR assay	ic50	0.0004	uM
4-[2-(3-amino-1,2-benzoxazol-5-yl)-4-chlorophenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1300000: Inhibition of full length human Nav1.7 channel expressed in HEK cells co-expressing human sodium channel subunit beta1 at holding potential -60 mV by automated voltage clamp analysis	ic50	0.0004	uM
4-(1-adamantylmethoxy)-N-(azetidin-1-ylsulfonyl)-5-cyclopropyl-2-fluorobenzamide	1420146: Inhibition of Nav1.7 (unknown origin) by electrophysiology assay	ic50	0.0004	uM
(4S)-4-amino-5-[[(2S)-1-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-65-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]-27,74-bis(4-aminobutyl)-24-(3-amino-3-oxopropyl)-68-[(5-bromo-1H-indol-3-yl)methyl]-33-butyl-4,54-bis(3-carbamimidamidopropyl)-13,51-bis(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36-bis(1H-indol-3-ylmethyl)-57-methyl-7,71-bis(2-methylpropyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontan-21-yl]amino]-1-oxopent-4-yn-2-yl]amino]-5-oxopentanoic acid	1363503: Inhibition of human Nav1.7 expressed in HEK293 cells at holding potential of -125 mV after 10 mins by patchxpress-based electrophysiology assay	ic50	0.0005	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-27,51,74-tris(4-aminobutyl)-24-(3-amino-3-oxopropyl)-21-[[(2S)-2-[[(2S)-2-aminopent-4-ynoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-33-butyl-4,54-bis(3-carbamimidamidopropyl)-13-(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36,68-tris(1H-indol-3-ylmethyl)-57-methyl-7,71-bis(2-methylpropyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontane-65-carbonyl]amino]pentanoyl]amino]hexanoyl]amino]-5-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	1363503: Inhibition of human Nav1.7 expressed in HEK293 cells at holding potential of -125 mV after 10 mins by patchxpress-based electrophysiology assay	ic50	0.0005	uM
2-[(1R,4S,10S,13S,16S,19S,22S,25R,30R,33S,36S,39S,42S,45S,48S,51R,54S,57S,60S,63S,66S,69S,72R,77R,80S,86S,89S,92S,95S)-77-[(2-aminoacetyl)amino]-30-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]carbamoyl]-42,60,69,92-tetrakis(4-aminobutyl)-4,16-bis(2-amino-2-oxoethyl)-22-(3-amino-3-oxopropyl)-89-benzyl-86-[(2S)-butan-2-yl]-36,45-bis(3-carbamimidamidopropyl)-39-[(1R)-1-hydroxyethyl]-13,48,63,66-tetrakis(hydroxymethyl)-33-(1H-indol-3-ylmethyl)-95-methyl-57,80-bis(2-methylpropyl)-2,3a,5,11,14,17,20,23,32,35,38,41,44,47,50,53,56,59,62,65,68,71,78,81,84,87,90,93,96-nonacosaoxo-54-propan-2-yl-a,27,28,74,75,99-hexathia-2a,3,6,12,15,18,21,24,31,34,37,40,43,46,49,52,55,58,61,64,67,70,79,82,85,88,91,94,97-nonacosazatetracyclo[49.46.4.225,72.06,10]trihectan-19-yl]acetic acid	1388450: Inhibition of human Nav1.7 expressed in HEK293 cells at -80 mV holding potential by QPatch assay	ic50	0.0005	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-27,51,74-tris(4-aminobutyl)-24-(3-amino-3-oxopropyl)-21-[[(2S)-2-[[(2S)-2-aminopent-4-ynoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-33-butyl-4,54-bis(3-carbamimidamidopropyl)-13-(2-carboxyethyl)-45-(carboxymethyl)-71-cyclohexyl-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36,68-tris(1H-indol-3-ylmethyl)-57-methyl-7-(2-methylpropyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontane-65-carbonyl]amino]pentanoyl]amino]hexanoyl]amino]-5-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	1363503: Inhibition of human Nav1.7 expressed in HEK293 cells at holding potential of -125 mV after 10 mins by patchxpress-based electrophysiology assay	ic50	0.0005	uM
(4S)-6-fluoro-4-[(2R,4S)-2-(4-fluorophenyl)-4-(trifluoromethyl)piperidin-1-yl]-N-pyrimidin-4-yl-3,4-dihydro-2H-chromene-7-sulfonamide	1420158: Binding affinity to recombinant human Nav1.7 after 18 hrs by radioligand binding assay	ic50	0.0005	uM
(4S)-6-fluoro-4-[(2R,4S)-2-(1H-pyrazol-4-yl)-4-(trifluoromethyl)piperidin-1-yl]-N-pyrimidin-4-yl-3,4-dihydro-2H-chromene-7-sulfonamide	1587784: Displacement of [3H]GX-545 from full length human Nav1.7 VSD4 domain expressed in HEK cell membranes measured after 20 hrs by liquid scintillation counting method	ki	0.0005	uM
(4R)-4-[2-(4-fluorophenyl)-4-(trifluoromethyl)phenyl]-N-(1,3-thiazol-2-yl)-3,4-dihydro-2H-chromene-7-sulfonamide	1668674: Inhibition of Nav1.7 (unknown origin) expressed in HEK293 cells assessed as reduction in veratridine-induced depolarization preincubated for 15 to 20 mins followed by veratridine stimulation by 1X red membrane potential dye based FLIPR assay	ic50	0.0005	uM
(4R)-N-(1,3-thiazol-2-yl)-4-[2-(triazol-1-yl)-4-(trifluoromethyl)phenyl]-3,4-dihydro-2H-chromene-7-sulfonamide	1668674: Inhibition of Nav1.7 (unknown origin) expressed in HEK293 cells assessed as reduction in veratridine-induced depolarization preincubated for 15 to 20 mins followed by veratridine stimulation by 1X red membrane potential dye based FLIPR assay	ic50	0.0005	uM
4-[4-chloro-2-[3-(methylamino)-1,2-benzoxazol-5-yl]phenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1300000: Inhibition of full length human Nav1.7 channel expressed in HEK cells co-expressing human sodium channel subunit beta1 at holding potential -60 mV by automated voltage clamp analysis	ic50	0.0005	uM
5-cyclopropyl-4-[[1-[(1S)-1-(3,5-dichlorophenyl)ethyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	1948697: Inhibition of human Nav1.7/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis	ic50	0.0006	uM
3-[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-65-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]carbamoyl]-27,57-bis(4-aminobutyl)-21-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-24-(3-amino-3-oxopropyl)-54,74-bis(3-carbamimidamidopropyl)-51-(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36,68-tris(1H-indol-3-ylmethyl)-71-(2-methylpropyl)-7,33-bis(2-methylsulfanylethyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-4-propan-2-yl-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontan-13-yl]propanoic acid	1183788: Inhibition of human Nav1.7 expressed in HEK-293 cells at -130 to -110 mV holding potential by whole-cell voltage clamp analysis	ic50	0.0006	uM
(4R)-N-(6-fluoro-2-pyridinyl)-4-[2-(2-methylpyrazol-3-yl)-4-(trifluoromethyl)phenyl]-3,4-dihydro-2H-chromene-7-sulfonamide	1668674: Inhibition of Nav1.7 (unknown origin) expressed in HEK293 cells assessed as reduction in veratridine-induced depolarization preincubated for 15 to 20 mins followed by veratridine stimulation by 1X red membrane potential dye based FLIPR assay	ic50	0.0006	uM
(4S)-4-[(2R,4S)-2-phenyl-4-(trifluoromethyl)piperidin-1-yl]-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-chromene-7-sulfonamide	1587750: Inhibition of full length human Nav1.7 expressed in HEK293 cells assessed as reduction of current amplitude at -60 mV holding potential measured after 20 mins by whole-cell voltage clamp method	ic50	0.0006	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-27,51,74-tris(4-aminobutyl)-24-(3-amino-3-oxopropyl)-21-[[(2S)-2-[[(2S)-2-aminopent-4-ynoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-33-butyl-4,54-bis(3-carbamimidamidopropyl)-13-(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-36,68-bis(1H-indol-3-ylmethyl)-57-methyl-7,71-bis(2-methylpropyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-30-(2-phenylethyl)-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontane-65-carbonyl]amino]pentanoyl]amino]hexanoyl]amino]-5-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	1363503: Inhibition of human Nav1.7 expressed in HEK293 cells at holding potential of -125 mV after 10 mins by patchxpress-based electrophysiology assay	ic50	0.0006	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-27,51,74-tris(4-aminobutyl)-24-(3-amino-3-oxopropyl)-21-[[(2S)-2-[[(2S)-2-aminopent-4-ynoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-33-butyl-4,54-bis(3-carbamimidamidopropyl)-13-(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36,68-tris(1H-indol-3-ylmethyl)-57-methyl-7,71-bis(2-methylpropyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontane-65-carbonyl]amino]pentanoyl]amino]hexanoyl]amino]-5-[[(2S)-1-amino-3-cyclohexyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1363503: Inhibition of human Nav1.7 expressed in HEK293 cells at holding potential of -125 mV after 10 mins by patchxpress-based electrophysiology assay	ic50	0.0006	uM
tert-butyl N-[(2R)-1-[[(3R)-1-(cyclopropylmethyl)-4-oxo-5-(2,2,2-trifluoroethyl)-2,3-dihydro-1,5-benzodiazepin-3-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate	314683: Inhibition of human Nav1.7 sodium channel expressed in HEK293 cells at a membrane potential of -70 mV by whole cell voltage clamp technique	ki	0.0006	uM
4-[2-[3-(azetidin-1-ylmethyl)phenyl]-4-iodophenoxy]-3-cyano-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	726420: Inhibition of NaV1.7 ion channel (unknown origin)	ic50	0.0006	uM
5-cyclopropyl-N-cyclopropylsulfonyl-2-fluoro-4-[(6-methylspiro[2.5]octan-6-yl)methoxy]benzamide	1960118: Inhibition of human Nav1.7 alpha subunit expressed in HEK293 cells co-expressing beta1 subunit at -60 mV holding potential by whole-cell patch voltage clamp electrophysiology recording	ic50	0.0006	uM
4-[4-chloro-2-[3-[(2-piperidin-4-ylethylamino)methyl]phenyl]phenoxy]-3-cyano-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1365864: Inhibition of human Nav1.7 expressed in HEK cells by automated patchXpress electrophysiology method	ic50	0.0007	uM
(4S)-6-fluoro-4-[(2R,4S)-2-pyridin-3-yl-4-(trifluoromethyl)piperidin-1-yl]-N-pyrimidin-4-yl-3,4-dihydro-2H-chromene-7-sulfonamide	1587784: Displacement of [3H]GX-545 from full length human Nav1.7 VSD4 domain expressed in HEK cell membranes measured after 20 hrs by liquid scintillation counting method	ki	0.0007	uM
4-[4-chloro-2-(2-piperazin-1-ylpyrimidin-4-yl)phenoxy]-3-cyano-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	726420: Inhibition of NaV1.7 ion channel (unknown origin)	ic50	0.0007	uM
4-[2-[3-(azetidin-1-ylmethyl)phenyl]-4-(trifluoromethyl)phenoxy]-3-cyano-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	726420: Inhibition of NaV1.7 ion channel (unknown origin)	ic50	0.0007	uM
4-[2-[2-(azetidin-3-yl)pyrazol-3-yl]-4-chlorophenoxy]-N-(5-chloro-1,3-thiazol-2-yl)-3-cyanobenzenesulfonamide	726420: Inhibition of NaV1.7 ion channel (unknown origin)	ic50	0.0007	uM
4-(cyclohexylmethoxy)-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	1960118: Inhibition of human Nav1.7 alpha subunit expressed in HEK293 cells co-expressing beta1 subunit at -60 mV holding potential by whole-cell patch voltage clamp electrophysiology recording	ic50	0.0007	uM
3-[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-65-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-anilino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]carbamoyl]-27,57-bis(4-aminobutyl)-21-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-24-(3-amino-3-oxopropyl)-54,74-bis(3-carbamimidamidopropyl)-51-(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36,68-tris(1H-indol-3-ylmethyl)-71-(2-methylpropyl)-7,33-bis(2-methylsulfanylethyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-4-propan-2-yl-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontan-13-yl]propanoic acid	1183788: Inhibition of human Nav1.7 expressed in HEK-293 cells at -130 to -110 mV holding potential by whole-cell voltage clamp analysis	ic50	0.0008	uM
(4S)-4-[(2R,4S)-2-(4-fluorophenyl)-4-(trifluoromethyl)piperidin-1-yl]-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-chromene-7-sulfonamide	1587784: Displacement of [3H]GX-545 from full length human Nav1.7 VSD4 domain expressed in HEK cell membranes measured after 20 hrs by liquid scintillation counting method	ki	0.0008	uM

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
sodium arsenite	affects methylation, affects splicing, decreases expression, affects cotreatment, increases abundance (+1 more)	6
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	5
Arsenic	increases abundance, increases expression, affects cotreatment, decreases expression	2
Carbamazepine	affects activity, affects response to substance	2
Doxorubicin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
bisphenol A	affects expression	1
terbufos	decreases methylation	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
picaridin	affects binding	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
incobotulinumtoxinA	increases expression	1
N-(2-methyl-3-(4-(4-(4-(trifluoromethoxy)benzyloxy)piperidin-1-yl)-1,3,5-triazin-2-ylamino)phenyl)acetamide	decreases activity	1
(+)-JQ1 compound	increases expression	1
Acetaminophen	increases expression	1
Caffeine	decreases phosphorylation	1
Cannabidiol	decreases activity	1
Cisplatin	affects cotreatment, decreases expression	1
Fonofos	decreases methylation	1
Malathion	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Mexiletine	increases response to substance	1
Nickel	increases expression	1

ChEMBL screening assays

428 unique, capped per target: 395 binding, 29 functional, 3 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3430568	Functional	Inhibition of Na channel (species unknown)	Simulation of multiple ion channel block provides improved early prediction of compounds’ clinical torsadogenic risk. — Cardiovasc Res
CHEMBL4880115	Binding	Na+ channel CEREP ligand profiling	Data for DCP probe A-079
CHEMBL4407433	ADMET	Inhibition of Nav1.7 (unknown origin)	Discovery of 3,4,6-Trisubstituted Piperidine Derivatives as Orally Active, Low hERG Blocking Akt Inhibitors via Conformational Restriction and Structure-Based Design. — J Med Chem

Cellosaurus cell lines

26 cell lines: 20 induced pluripotent stem cell, 3 transformed cell line, 2 spontaneously immortalized cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_9S31	PFIZi001-A	Induced pluripotent stem cell	Female
CVCL_9S32	PFIZi002-A	Induced pluripotent stem cell	Female
CVCL_9S33	PFIZi003-A	Induced pluripotent stem cell	Male
CVCL_9S34	PFIZi004-A	Induced pluripotent stem cell	Male
CVCL_9S41	RCi001-A	Induced pluripotent stem cell	Male
CVCL_9S42	RCi001-B	Induced pluripotent stem cell	Male
CVCL_9S43	RCi002-A	Induced pluripotent stem cell	Female
CVCL_9S44	RCi002-B	Induced pluripotent stem cell	Female
CVCL_A5MX	UKAi005-A	Induced pluripotent stem cell	Female
CVCL_A5MY	UKAi006-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

405 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy