Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T43739 Target Info
Target Name Voltage-gated sodium channel alpha Nav1.8 (SCN10A)
Synonyms hPN3; Voltage-gated sodium channel subunit alpha Nav1.8; Sodium channel protein type X subunit alpha; Sodium channel protein type 10 subunit alpha; Peripheral nerve sodium channel 3; PN3
Target Type Successful Target
Gene Name SCN10A
Biochemical Class Voltage-gated ion channel
UniProt ID
SCNAA_HUMAN
Ligand General Information  Top
Ligand Name Lpc-Ether Ligand Info
Canonical SMILES CCCCCCCCCCCCCCCCCCOCC(COP(=O)([O-])OCC[N+](C)(C)C)O
InChI 1S/C26H56NO6P/c1-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-22-31-24-26(28)25-33-34(29,30)32-23-21-27(2,3)4/h26,28H,5-25H2,1-4H3/t26-/m1/s1
InChIKey XKBJVQHMEXMFDZ-AREMUKBSSA-N
PubChem Compound ID 2733532
Drug Binding Sites of Target  Top
PDB ID: 7WE4      Human Nav1.8 with A-803467, class I
Method Electron microscopy Resolution 2.70 Å Mutation No [1]
PDB Sequence
LIRRTAIKVS
127
VHSWFSLFIT
137
VTILVNCVCM
147
TRTDLPEKIE
157
YVFTVIYTFE
167

ALIKILARGF
177
CLNEFTYLRD
187
PWNWLDFSVI
197
TLAYVGTAID
207
LRGISGLRTF
217

RVLRALKTVS
227
VIPGLKVIVG
237
ALIHSVKKLA
247
DVTILTIFCL
257
SVFALVGLQL
267

FKGNLKNKCV
277
KNDMAYSSHR
293
KPDIYINKRG
303
TSDPLLCGNG
313
SDSGHCPDGY
323

ICLKTSDNPD
333
FNYTSFDSFA
343
WAFLSLFRLM
353
TQDSWERLYQ
363
QTLRTSGKIY
373

MIFFVLVIFL
383
GSFYLVNLIL
393
AVVTMAYEEQ
403
NQATWVKLKT
656
ILFGLVTDPF
666

AELTITLCIV
676
VNTIFMAMEH
686
HGMSPTFEAM
696
LQIGNIVFTI
706
FFTAEMVFKI
716

IAFDPYYYFQ
726
KKWNIFDCII
736
VTVSLLELGV
746
AKKGSLSVLR
756
SFRLLRVFKL
766

AKSWPTLNTL
776
IKIIGNSVGA
786
LGNLTIILAI
796
IVFVFALVGK
806
QLLGENYRNN
816

RKNISAPHED
826
WPRWHMHDFF
836
HSFLIVFRIL
846
CGEWIENMWA
856
CMEVGQKSIC
866

LILFLTVMVL
876
GNLVVLNLFI
886
ALLLNSFFAD
1136
VGWQVRKTCY
1146
RIVEHSWFES
1156

FIIFMILLSS
1166
GSLAFEDYYL
1176
DQKPTVKALL
1186
EYTDRVFTFI
1196
FVFEMLLKWV
1206

AYGFKKYFTN
1216
AWCWLDFLIV
1226
NISLISLTAK
1236
ILEYSEVAPI
1246
KALRTLRALR
1256

PLRALSRFEG
1266
MRVVVDALVG
1276
AIPSIMNVLL
1286
VCLIFWLIFS
1296
IMGVNLFAGK
1306

FWRCINYTDG
1316
EFSLVPLSIV
1326
NNKSDCKIQN
1336
STGSFFWVNV
1346
KVNFDNVAMG
1356

YLALLQVATF
1366
KGWMDIMYAA
1376
VDSREVNMQP
1386
KWEDNVYMYL
1396
YFVIFIIFGG
1406

FFTLNLFVGV
1416
IIDNFNQQKK
1426
KLGGQDIFMT
1436
EEQKKYYNAM
1446
KKLGSKKPQK
1456

PIPRPLNKFQ
1466
GFVFDIVTRQ
1476
AFDITIMVLI
1486
CLNMITMMVE
1496
TDDQSEEKTK
1506

ILGKINQFFV
1516
AVFTGECVMK
1526
MFALRQYYFT
1536
NGWNVFDFIV
1546
VVLSIASLIF
1556

SAILKSLQSY
1566
FSPTLFRVIR
1576
LARIGRILRL
1586
IRAAKGIRTL
1596
LFALMMSLPA
1606

LFNIGLLLFL
1616
VMFIYSIFGM
1626
SSFPHVRWEA
1636
GIDDMFNFQT
1646
FANSMLCLFQ
1656

ITTSAGWDGL
1666
LSPILNTGPP
1676
YCDPNLPNSN
1686
GTRGDCGSPA
1696
VGIIFFTTYI
1706

IISFLIMVNM
1716
YIAVILENFN
1726
VA
Residue
Distance (Å)
PHE260
4.788
VAL263
4.060
LEU267
4.429
ILE372
4.163
TYR373
3.876
ILE375
4.523
PHE376
3.763
LEU379
3.869
PHE382
4.295
VAL677
4.556
ILE680
3.020
PHE681
4.267
MET684
3.377
HIS686
4.463
SER690
3.161
THR692
2.433
PHE693
4.309
MET696
3.936
ILE780
3.851
SER783
3.800
VAL784
3.353
THR791
3.989
LEU794
3.888
PHE843
3.532
LEU846
3.424
CYS847
4.147
VAL881
3.832
LEU884
3.705
LEU1163
4.609
SER1166
3.712
GLY1167
3.441
ALA1170
2.670
PHE1171
2.831
ASP1173
4.136
ASN1216
3.374
ALA1217
3.547
TRP1218
3.626
LEU1221
4.597
LEU1255
4.061
PRO1257
4.636
LEU1258
4.619
Residue
Distance (Å)
ALA1260
4.811
LEU1261
4.497
VAL1271
4.840
ASP1272
4.338
VAL1275
4.648
LEU1289
4.304
ALA1354
4.066
TYR1357
4.203
PHE1366
3.861
ILE1402
3.642
ILE1403
3.503
PHE1404
3.894
GLY1406
4.983
PHE1407
3.275
PHE1408
3.746
LEU1410
4.941
GLU1438
4.821
GLN1439
3.210
TYR1442
3.824
ALA1445
4.368
MET1446
4.098
LEU1449
3.257
PHE1567
2.522
SER1568
3.354
THR1570
3.584
LEU1571
3.092
VAL1574
3.275
LEU1577
4.428
MET1601
4.723
LEU1604
4.117
PRO1605
3.527
LEU1607
3.916
PHE1608
3.844
GLY1611
3.882
LEU1614
4.751
PHE1615
3.603
LEU1616
3.291
PHE1619
3.705
PHE1647
3.331
MET1716
3.840
PDB ID: 7WFR      Human Nav1.8 with A-803467, class III
Method Electron microscopy Resolution 3.00 Å Mutation No [1]
PDB Sequence
SWFSLFITVT
139
ILVNCVCMTR
149
TDLPEKIEYV
159
FTVIYTFEAL
169
IKILARGDPW
189

NWLDFSVITL
199
AYVGTAIDLR
209
GISGLRTFRV
219
LRALKTVSVI
229
PGLKVIVGAL
239

IHSVKKLADV
249
TILTIFCLSV
259
FALVGLQLFK
269
GNLKNKCVKN
279
DMAYSSHRKP
295

DIYINKRGTS
305
DPLLCGNGSD
315
SGHCPDGYIC
325
LKTSDNPDFN
335
YTSFDSFAWA
345

FLSLFRLMTQ
355
DSWERLYQQT
365
LRTSGKIYMI
375
FFVLVIFLGS
385
FYLVNLILAV
395

VTMAYEEQNQ
405
ATWVKLKTIL
658
FGLVTDPFAE
668
LTITLCIVVN
678
TIFMAMEHHG
688

MSPTFEAMLQ
698
IGNIVFTIFF
708
TAEMVFKIIA
718
FDPYYYFQKK
728
WNIFDCIIVT
738

VSLLELGVAK
748
KGSLSVLRSF
758
RLLRVFKLAK
768
SWPTLNTLIK
778
IIGNSVGALG
788

NLTIILAIIV
798
FVFALVGKQL
808
LGENYRNNRK
818
NISAPHEDWP
828
RWHMHDFFHS
838

FLIVFRILCG
848
EWIENMWACM
858
EVGQKSICLI
868
LFLTVMVLGN
878
LVVLNLFIAL
888

LLNSFFADVG
1138
WQVRKTCYRI
1148
VEHSWFESFI
1158
IFMILLSSGS
1168
LAFEDYYLDQ
1178

KPTVKALLEY
1188
TDRVFTFIFV
1198
FEMLLKWVAY
1208
GFKKYFTNAW
1218
CWLDFLIVNI
1228

SLISLTAKIL
1238
EYSEVAPIKA
1248
LRTLRALRPL
1258
RALSRFEGMR
1268
VVVDALVGAI
1278

PSIMNVLLVC
1288
LIFWLIFSIM
1298
GVNLFAGKFW
1308
RCINYTDGEF
1318
SLVPLSIVNN
1328

KSDCKIQNST
1338
GSFFWVNVKV
1348
NFDNVAMGYL
1358
ALLQVATFKG
1368
WMDIMYAAVD
1378

SREVNMQPKW
1388
EDNVYMYLYF
1398
VIFIIFGGFF
1408
TLNLFVGVII
1418
DNFNQQKKKL
1428

GGQDIFMTEE
1438
QKKYYNAMKK
1448
LGSKKPQKPI
1458
PRPLNKFQGF
1468
VFDIVTRQAF
1478

DITIMVLICL
1488
NMITMMVETD
1498
DQSEEKTKIL
1508
GKINQFFVAV
1518
FTGECVMKMF
1528

ALRQYYFTNG
1538
WNVFDFIVVV
1548
LSIASLIFSA
1558
ILKSLQSYFS
1568
PTLFRVIRLA
1578

RIGRILRLIR
1588
AAKGIRTLLF
1598
ALMMSLPALF
1608
NIGLLLFLVM
1618
FIYSIFGMSS
1628

FPHVRWEAGI
1638
DDMFNFQTFA
1648
NSMLCLFQIT
1658
TSAGWDGLLS
1668
PILNTGPPYC
1678

DPNLPNSNGT
1688
RGDCGSPAVG
1698
IIFFTTYIII
1708
SFLIMVNMYI
1718
AVILENFNVA
1728
Residue
Distance (Å)
VAL243
3.456
LYS244
3.568
LEU246
3.847
ALA247
3.210
THR250
3.464
ILE251
3.599
ILE254
3.904
PHE260
4.892
VAL263
4.021
LEU267
4.273
ILE372
4.092
TYR373
3.738
ILE375
4.045
PHE376
3.986
LEU379
3.430
PHE382
4.158
THR672
4.334
LEU673
4.089
VAL676
4.463
VAL677
4.540
ILE680
3.871
PHE681
4.772
MET684
3.683
HIS686
4.289
SER690
3.451
THR692
3.708
PHE693
3.683
MET696
3.432
ILE780
3.871
SER783
3.229
VAL784
3.032
THR791
3.468
LEU794
3.810
PHE843
3.453
LEU846
3.620
CYS847
4.396
VAL875
4.108
VAL881
3.647
LEU884
3.515
LEU1163
4.920
SER1166
4.135
GLY1167
3.701
ALA1170
2.827
PHE1171
2.953
ASP1173
4.475
ASN1216
3.338
Residue
Distance (Å)
ALA1217
3.839
TRP1218
3.451
LEU1221
4.250
LEU1252
4.483
LEU1255
3.904
PRO1257
4.842
LEU1258
3.946
ALA1260
4.997
VAL1271
4.121
ASP1272
3.585
VAL1275
4.349
LEU1289
4.349
ASN1352
4.383
ALA1354
4.020
TYR1357
4.093
PHE1366
4.124
ILE1402
4.031
ILE1403
3.364
PHE1404
4.291
PHE1407
3.182
PHE1408
3.979
LEU1410
4.471
GLN1439
4.151
TYR1442
3.031
SER1568
2.923
THR1570
3.050
LEU1571
3.379
VAL1574
3.534
LEU1577
4.486
ALA1589
3.719
ALA1590
4.444
LYS1591
3.510
GLY1592
4.086
MET1601
4.764
LEU1604
3.501
PRO1605
3.263
LEU1607
3.992
PHE1608
3.806
GLY1611
4.018
PHE1615
3.555
LEU1616
3.715
PHE1619
3.578
THR1646
4.728
PHE1647
3.255
MET1716
3.669
PDB ID: 7WFW      Apo human Nav1.8
Method Electron microscopy Resolution 3.10 Å Mutation No [1]
PDB Sequence
LKVIVGALIH
241
SVKKLADVTI
251
LTIFCLSVFA
261
LVGLQLFKGN
271
LKNKCVKNDP
295

DIYINKRGTS
305
DPLLCGNGSD
315
SGHCPDGYIC
325
LKTSDNPDFN
335
YTSFDSFAWA
345

FLSLFRLMTQ
355
DSWERLYQQT
365
LRTSGKIYMI
375
FFVLVIFLGS
385
FYLVNLILAV
395

VTMAYEEQNQ
405
ATWVKLKTIL
658
FGLVTDPFAE
668
LTITLCIVVN
678
TIFMAMEHHG
688

MSPTFEAMLQ
698
IGNIVFTIFF
708
TAEMVFKIIA
718
FDPYYYFQKK
728
WNIFDCIIVT
738

VSLLELGVAK
748
KGSLSVLRSF
758
RLLRVFKLAK
768
SWPTLNTLIK
778
IIGNSVGALG
788

NLTIILAIIV
798
FVFALVGKQL
808
LGENYRNNRK
818
NISAPHEDWP
828
RWHMHDFFHS
838

FLIVFRILCG
848
EWIENMWACM
858
EVGQKSICLI
868
LFLTVMVLGN
878
LVVLNLFIAL
888

LLNSFFADVG
1138
WQVRKTCYRI
1148
VEHSWFESFI
1158
IFMILLSSGS
1168
LAFEDYYLDQ
1178

KPTVKALLEY
1188
TDRVFTFIFV
1198
FEMLLKWVAY
1208
GFKKYFTNAW
1218
CWLDFLIVNI
1228

SLISLTAKIL
1238
EYSEVAPIKA
1248
LRTLRALRPL
1258
RALSRFEGMR
1268
VVVDALVGAI
1278

PSIMNVLLVC
1288
LIFWLIFSIM
1298
GVNLFAGKFW
1308
RCINYTDGEF
1318
SLVPLSIVNN
1328

KSDCKIQNST
1338
GSFFWVNVKV
1348
NFDNVAMGYL
1358
ALLQVATFKG
1368
WMDIMYAAVD
1378

SREVNMQPKW
1388
EDNVYMYLYF
1398
VIFIIFGGFF
1408
TLNLFVGVII
1418
DNFNQQKKKL
1428

GGQDIFMTEE
1438
QKKYYNAMKK
1448
LGSKKPQKPI
1458
PRPLNKFQGF
1468
VFDIVTRQAF
1478

DITIMVLICL
1488
NMITMMVETD
1498
DQSEEKTKIL
1508
GKINQFFVAV
1518
FTGECVMKMF
1528

ALRQYYFTNG
1538
WNVFDFIVVV
1548
LSIASLIFSA
1558
ILKSLQSYFS
1568
PTLFRVIRLA
1578

RIGRILRLIR
1588
AAKGIRTLLF
1598
ALMMSLPALF
1608
NIGLLLFLVM
1618
FIYSIFGMSS
1628

FPHVRWEAGI
1638
DDMFNFQTFA
1648
NSMLCLFQIT
1658
TSAGWDGLLS
1668
PILNTGPPYC
1678

DPNLPNSNGT
1688
RGDCGSPAVG
1698
IIFFTTYIII
1708
SFLIMVNMYI
1718
AVILENFN
Residue
Distance (Å)
VAL263
4.546
LEU267
4.196
ILE372
3.572
TYR373
3.362
ILE375
4.313
PHE376
4.280
LEU379
4.263
PHE382
4.300
THR672
3.907
LEU673
4.904
VAL676
4.361
VAL677
4.176
ILE680
3.450
PHE681
4.922
MET684
4.120
HIS686
4.440
SER690
4.480
THR692
3.722
PHE693
2.666
MET696
4.132
LEU1163
4.374
SER1166
3.969
GLY1167
3.327
ALA1170
2.575
PHE1171
2.909
ASP1173
4.216
ASN1216
2.642
ALA1217
3.107
TRP1218
3.239
LEU1221
4.080
LEU1252
4.202
LEU1255
3.603
PRO1257
4.633
Residue
Distance (Å)
LEU1258
3.933
ALA1260
4.720
VAL1271
4.248
ASP1272
4.180
VAL1275
4.351
LEU1289
3.756
ASN1352
4.486
ALA1354
4.259
TYR1357
4.132
GLU1438
4.846
GLN1439
3.474
TYR1442
3.334
ALA1445
4.344
MET1446
3.896
SER1568
2.835
THR1570
3.624
LEU1571
4.229
VAL1574
2.986
LEU1577
4.560
MET1601
4.695
LEU1604
3.233
PRO1605
3.604
LEU1607
3.763
PHE1608
3.849
GLY1611
3.970
LEU1612
4.910
PHE1615
3.803
LEU1616
3.817
PHE1619
2.591
THR1646
4.894
PHE1647
3.359
MET1716
2.483
PDB ID: 7WEL      Human Nav1.8 with A-803467, class II
Method Electron microscopy Resolution 3.20 Å Mutation No [1]
PDB Sequence
HSWFSLFITV
138
TILVNCVCMT
148
RTDLPEKIEY
158
VFTVIYTFEA
168
LIKILARGFD
187

PWNWLDFSVI
197
TLAYVGTAID
207
LRGISGLRTF
217
RVLRALKTVS
227
VIPGLKVIVG
237

ALIHSVKKLA
247
DVTILTIFCL
257
SVFALVGLQL
267
FKGNLKNKCV
277
KNDMAYSSHR
293

KPDIYINKRG
303
TSDPLLCGNG
313
SDSGHCPDGY
323
ICLKTSDNPD
333
FNYTSFDSFA
343

WAFLSLFRLM
353
TQDSWERLYQ
363
QTLRTSGKIY
373
MIFFVLVIFL
383
GSFYLVNLIL
393

AVVTMAYEEQ
403
NQATWVKLKT
656
ILFGLVTDPF
666
AELTITLCIV
676
VNTIFMAMEH
686

HGMSPTFEAM
696
LQIGNIVFTI
706
FFTAEMVFKI
716
IAFDPYYYFQ
726
KKWNIFDCII
736

VTVSLLELGV
746
AKKGSLSVLR
756
SFRLLRVFKL
766
AKSWPTLNTL
776
IKIIGNSVGA
786

LGNLTIILAI
796
IVFVFALVGK
806
QLLGENYRNN
816
RKNISAPHED
826
WPRWHMHDFF
836

HSFLIVFRIL
846
CGEWIENMWA
856
CMEVGQKSIC
866
LILFLTVMVL
876
GNLVVLNLFI
886

ALLLNSFFAD
1136
VGWQVRKTCY
1146
RIVEHSWFES
1156
FIIFMILLSS
1166
GSLAFEDYYL
1176

DQKPTVKALL
1186
EYTDRVFTFI
1196
FVFEMLLKWV
1206
AYGFKKYFTN
1216
AWCWLDFLIV
1226

NISLISLTAK
1236
ILEYSEVAPI
1246
KALRTLRALR
1256
PLRALSRFEG
1266
MRVVVDALVG
1276

AIPSIMNVLL
1286
VCLIFWLIFS
1296
IMGVNLFAGK
1306
FWRCINYTDG
1316
EFSLVPLSIV
1326

NNKSDCKIQN
1336
STGSFFWVNV
1346
KVNFDNVAMG
1356
YLALLQVATF
1366
KGWMDIMYAA
1376

VDSREVNMQP
1386
KWEDNVYMYL
1396
YFVIFIIFGG
1406
FFTLNLFVGV
1416
IIDNFNQQKK
1426

KLGGQDIFMT
1436
EEQKKYYNAM
1446
KKLGSKKPQK
1456
PIPRPLNKFQ
1466
GFVFDIVTRQ
1476

AFDITIMVLI
1486
CLNMITMMVE
1496
TDDQSEEKTK
1506
ILGKINQFFV
1516
AVFTGECVMK
1526

MFALRQYYFT
1536
NGWNVFDFIV
1546
VVLSIASLIF
1556
SAILKSLQSY
1566
FSPTLFRVIR
1576

LARIGRILRL
1586
IRAAKGIRTL
1596
LFALMMSLPA
1606
LFNIGLLLFL
1616
VMFIYSIFGM
1626

SSFPHVRWEA
1636
GIDDMFNFQT
1646
FANSMLCLFQ
1656
ITTSAGWDGL
1666
LSPILNTGPP
1676

YCDPNLPNSN
1686
GTRGDCGSPA
1696
VGIIFFTTYI
1706
IISFLIMVNM
1716
YIAVILENFN
1726

VA
Click to Show 3D Structure of This Binding Site
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Residue
Distance (Å)
VAL243
3.540
LYS244
3.681
LEU246
3.747
ALA247
3.432
THR250
3.182
ILE251
3.685
ILE254
3.865
PHE260
4.766
VAL263
4.017
LEU267
4.518
ILE372
3.737
TYR373
3.709
ILE375
3.495
PHE376
3.663
LEU379
4.183
PHE382
3.711
ILE680
2.788
PHE681
4.171
MET684
3.849
HIS686
4.674
SER690
3.390
THR692
2.712
PHE693
3.930
MET696
4.290
VAL875
3.895
LEU1163
4.615
SER1166
3.592
GLY1167
3.356
ALA1170
2.656
PHE1171
2.383
ASP1173
3.936
ASN1216
3.096
ALA1217
3.829
TRP1218
3.726
LEU1221
4.766
LEU1252
4.150
LEU1255
3.830
Residue
Distance (Å)
PRO1257
4.468
LEU1258
4.333
ALA1260
4.436
ARG1268
4.996
VAL1271
4.427
VAL1275
4.342
LEU1289
4.073
ASN1352
4.619
ALA1354
4.079
TYR1357
3.855
GLN1439
4.250
TYR1442
3.771
ALA1445
4.488
MET1446
4.616
LEU1449
3.889
SER1568
3.129
THR1570
3.363
LEU1571
3.658
VAL1574
3.494
LEU1577
4.579
ALA1589
4.860
ALA1590
4.135
LYS1591
3.352
GLY1592
3.652
MET1601
4.147
LEU1604
4.042
PRO1605
3.403
LEU1607
3.829
PHE1608
3.741
GLY1611
3.849
LEU1614
4.972
PHE1615
4.321
LEU1616
3.138
PHE1619
4.009
THR1646
4.650
PHE1647
3.305
MET1716
4.141
References  Top
REF 1 Structural basis for high-voltage activation and subtype-specific inhibition of human Na(v)1.8. Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2208211119.

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