General Information of Drug Transporter (DTP) (ID: DTQC85B)

DTP Name Voltage-gated sodium channel alpha Nav1.7 (SCN9A)
Gene Name SCN9A
UniProt ID
Q15858 (SCN9A_HUMAN)
VARIDT ID
DTD0529
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Synonyms
ETHA; FEB3B; GEFSP7; HSAN2D; NE-NA; NENA; Nav1.7; Neuroendocrine sodium channel; PN1; Peripheral sodium channel 1; SCN9A; SFNP; Sodium channel protein type IX subunit alpha; Sodium channel protein type 9 subunit alpha; hNE-Na; Voltage-gated sodium channel subunit alpha Nav1.7
DTP Family Voltage-Gated Ion Channel (VIC) Superfamily ;
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. Isoform 1 is expressedpreferentially in the central and peripheral nervous system.Isoform 2 is expressed preferentially in the dorsal root ganglion.
Sequence
MAMLPPPGPQSFVHFTKQSLALIEQRIAERKSKEPKEEKKDDDEEAPKPSSDLEAGKQLP
FIYGDIPPGMVSEPLEDLDPYYADKKTFIVLNKGKTIFRFNATPALYMLSPFSPLRRISI
KILVHSLFSMLIMCTILTNCIFMTMNNPPDWTKNVEYTFTGIYTFESLVKILARGFCVGE
FTFLRDPWNWLDFVVIVFAYLTEFVNLGNVSALRTFRVLRALKTISVIPGLKTIVGALIQ
SVKKLSDVMILTVFCLSVFALIGLQLFMGNLKHKCFRNSLENNETLESIMNTLESEEDFR
KYFYYLEGSKDALLCGFSTDSGQCPEGYTCVKIGRNPDYGYTSFDTFSWAFLALFRLMTQ
DYWENLYQQTLRAAGKTYMIFFVVVIFLGSFYLINLILAVVAMAYEEQNQANIEEAKQKE
LEFQQMLDRLKKEQEEAEAIAAAAAEYTSIRRSRIMGLSESSSETSKLSSKSAKERRNRR
KKKNQKKLSSGEEKGDAEKLSKSESEDSIRRKSFHLGVEGHRRAHEKRLSTPNQSPLSIR
GSLFSARRSSRTSLFSFKGRGRDIGSETEFADDEHSIFGDNESRRGSLFVPHRPQERRSS
NISQASRSPPMLPVNGKMHSAVDCNGVVSLVDGRSALMLPNGQLLPEVIIDKATSDDSGT
TNQIHKKRRCSSYLLSEDMLNDPNLRQRAMSRASILTNTVEELEESRQKCPPWWYRFAHK
FLIWNCSPYWIKFKKCIYFIVMDPFVDLAITICIVLNTLFMAMEHHPMTEEFKNVLAIGN
LVFTGIFAAEMVLKLIAMDPYEYFQVGWNIFDSLIVTLSLVELFLADVEGLSVLRSFRLL
RVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYKECVCKIN
DDCTLPRWHMNDFFHSFLIVFRVLCGEWIETMWDCMEVAGQAMCLIVYMMVMVIGNLVVL
NLFLALLLSSFSSDNLTAIEEDPDANNLQIAVTRIKKGINYVKQTLREFILKAFSKKPKI
SREIRQAEDLNTKKENYISNHTLAEMSKGHNFLKEKDKISGFGSSVDKHLMEDSDGQSFI
HNPSLTVTVPIAPGESDLENMNAEELSSDSDSEYSKVRLNRSSSSECSTVDNPLPGEGEE
AEAEPMNSDEPEACFTDGCVWRFSCCQVNIESGKGKIWWNIRKTCYKIVEHSWFESFIVL
MILLSSGALAFEDIYIERKKTIKIILEYADKIFTYIFILEMLLKWIAYGYKTYFTNAWCW
LDFLIVDVSLVTLVANTLGYSDLGPIKSLRTLRALRPLRALSRFEGMRVVVNALIGAIPS
IMNVLLVCLIFWLIFSIMGVNLFAGKFYECINTTDGSRFPASQVPNRSECFALMNVSQNV
RWKNLKVNFDNVGLGYLSLLQVATFKGWTIIMYAAVDSVNVDKQPKYEYSLYMYIYFVVF
IIFGSFFTLNLFIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAMKKLGSKKPQKPIPRP
GNKIQGCIFDLVTNQAFDISIMVLICLNMVTMMVEKEGQSQHMTEVLYWINVVFIILFTG
ECVLKLISLRHYYFTVGWNIFDFVVVIISIVGMFLADLIETYFVSPTLFRVIRLARIGRI
LRLVKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGMSNFAYVKKEDGINDMFN
FETFGNSMICLFQITTSAGWDGLLAPILNSKPPDCDPKKVHPGSSVEGDCGNPSVGIFYF
VSYIIISFLVVVNMYIAVILENFSVATEESTEPLSEDDFEMFYEVWEKFDPDATQFIEFS
KLSDFAAALDPPLLIAKPNKVQLIAMDLPMVSGDRIHCLDILFAFTKRVLGESGEMDSLR
SQMEERFMSANPSKVSYEPITTTLKRKQEDVSATVIQRAYRRYRLRQNVKNISSIYIKDG
DRDDDLLNKKDMAFDNVNENSSPEKTDATSSTTSPPSYDSVTKPDKEKYEQDRTEKEDKG
KDSKESKK
Function
This transporter plays a role in inflammatory pain mechanisms and mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform).
Endogenous Substrate(s) Na+
TCDB ID
1.A.1.10.5
Gene ID
6335
KEGG Pathway
Taste transduction (hsa04742 )
Reactome Pathway
Phase 0 - rapid depolarisation (R-HSA-5576892 )
Sensory perception of sweet, bitter, and umami (glutamate) taste (R-HSA-9717207 )
Interaction between L1 and Ankyrins (R-HSA-445095 )

The Drug Therapeutic Target (DTT) Role of This DTP

DTP DTT Name Voltage-gated sodium channel alpha Nav1.7 (SCN9A) DTT Info
DTP DTT Type Clinical trial
12 Clinical Trial Drug(s) Targeting This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
BIIB074 DMLV1ET Bipolar disorder 6A60 Phase 2 [1]
PF-05089771 DMD74BJ Chronic pain MG30 Phase 2 [2]
XEN-402 DMR69CG Osteoarthritis FA00-FA05 Phase 2 [3]
BIIB095 DMUC6EP Pain MG30-MG3Z Phase 1 [1]
CC8464 DMILHMC Neuropathic pain 8E43.0 Phase 1 [1]
DSP-2230 DM0WTMD Neuropathic pain 8E43.0 Phase 1 [1]
DSP-3905 DMYHU24 Neuropathic pain 8E43.0 Phase 1 [1]
DWJ-208 DMQKDJZ Cancer related pain MG30 Phase 1 [1]
GDC0310 DMUNFEP Chronic pain MG30 Phase 1 [4]
PF-05186462 DMUF6W9 Pain MG30-MG3Z Phase 1 [5]
PF-05241328 DM2NTBL Pain MG30-MG3Z Phase 1 [6]
RG7893 DM1R4MQ Pain MG30-MG3Z Phase 1 [7]
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⏷ Show the Full List of 12 Clinical Trial Drug(s)
19 Patented Agent(s) Targeting This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
Aryl carboxamide derivative 1 DMTZRCW N. A. N. A. Patented [8]
Aryl carboxamide derivative 2 DM146TA N. A. N. A. Patented [8]
Aryl carboxamide derivative 4 DMNBW8P N. A. N. A. Patented [8]
Benzene sulfonamide derivative 11 DML9TF7 N. A. N. A. Patented [8]
Benzene sulfonamide derivative 12 DMESKY1 N. A. N. A. Patented [8]
Benzene sulfonamide derivative 15 DMFJTE9 N. A. N. A. Patented [8]
Benzene sulfonamide derivative 9 DMLET14 N. A. N. A. Patented [8]
Cyclopropyl-spiro piperidine derivative 1 DM0YTGS N. A. N. A. Patented [8]
Cyclopropyl-spiro piperidine derivative 2 DMM0R65 N. A. N. A. Patented [8]
Cyclopropyl-spiro piperidine derivative 3 DM0IZW8 N. A. N. A. Patented [8]
Cyclopropyl-spiro piperidine derivative 4 DM2ZWSM N. A. N. A. Patented [8]
Dihydrobenzoxazine and tetrahydroquinoxaline sulfonamide derivative 1 DMUNFAT N. A. N. A. Patented [8]
Enzoxazolinone sulfonamide derivative 1 DMJSIN8 N. A. N. A. Patented [8]
Methylsulfonylbenzamide derivative 2 DMHVZ4M N. A. N. A. Patented [8]
Pyrimidine derivative 1 DMN9VQM N. A. N. A. Patented [8]
Pyrrolo-benzo-diazine derivative 1 DMS4I6B N. A. N. A. Patented [8]
Pyrrolo-pyridinone derivative 5 DMK2FSY N. A. N. A. Patented [8]
Pyrrolo-pyridinone derivative 6 DMXGNP8 N. A. N. A. Patented [8]
Tarizine derivative 1 DMK5HAC N. A. N. A. Patented [8]
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⏷ Show the Full List of 19 Patented Agent(s)
3 Discontinued Drug(s) Targeting This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
Corus 1030 DMRVJ1A Asthma CA23 Discontinued in Phase 2 [9]
SIPATRIGINE DMMQ4GC Neurological disorder 6B60 Discontinued in Phase 2 [10]
V-102862 DMR2EUV N. A. N. A. Discontinued in Phase 1 [11]
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8 Investigative Drug(s) Targeting This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
4-(2'-(trifluoromethoxy)biphenyl-3-yl)oxazole DMIL45X Discovery agent N.A. Investigative [11]
4-(2'-(trifluoromethoxy)biphenyl-3-yl)thiazole DM3R2D1 Discovery agent N.A. Investigative [11]
4-(2'-(trifluoromethyl)biphenyl-3-yl)oxazole DMXC5S0 Discovery agent N.A. Investigative [11]
batrachotoxin DMYH9SU Discovery agent N.A. Investigative [12]
N-Me-aminopyrimidinone 9 DMM731A Discovery agent N.A. Investigative [13]
pyrrolopyrimidine 48 DMUEKB3 Discovery agent N.A. Investigative [14]
veratridine DMUF8JZ Discovery agent N.A. Investigative [12]
XEN-907 DMZ24P1 Pain MG30-MG3Z Investigative [12]
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⏷ Show the Full List of 8 Investigative Drug(s)

References

1 Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
2 Primary erythromelalgia: a review. Orphanet J Rare Dis. 2015 Sep 30;10:127.
3 Treatment of Na(v)1.7-mediated pain in inherited erythromelalgia using a novel sodium channel blocker. Pain. 2012 Jan;153(1):80-5.
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026875)
6 Recent progress in sodium channel modulators for pain. Bioorg Med Chem Lett. 2014 Aug 15;24(16):3690-9.
7 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800041740)
8 Sodium channel blockers: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015 Mar;25(3):279-90.
9 Differential modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by the local anesthetic lidocaine. Br J Pharmacol. 2004 Jun;142(3):576-84.
10 Oxadiazolylindazole sodium channel modulators are neuroprotective toward hippocampal neurones. J Med Chem. 2009 May 14;52(9):2694-707.
11 Substituted biaryl oxazoles, imidazoles, and thiazoles as sodium channel blockers. Bioorg Med Chem Lett. 2010 Sep 15;20(18):5536-40.
12 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 584).
13 Discovery and optimization of aminopyrimidinones as potent and state-dependent Nav1.7 antagonists. Bioorg Med Chem Lett. 2012 Jan 15;22(2):1055-60.
14 Discovery and hit-to-lead optimization of pyrrolopyrimidines as potent, state-dependent Na(v)1.7 antagonists. Bioorg Med Chem Lett. 2012 Mar 1;22(5):2052-62.