Target Information

Target General Infomation
Target ID
T43739
Former ID
TTDS00514
Target Name
Voltage-gated sodium channel subunit alpha Nav1.8
Gene Name
SCN10A
Synonyms
PN3; SNS; TTX-R sodium channel; TTX-R/NaV1.8; Transient tetrodotoxin-resistant Na+ current; Voltage-gated sodium channel NaV1.8; SCN10A
Target Type
Successful
Disease Asthma [ICD10: J45]
Anesthesia [ICD9: 338; ICD10: R20.0]
Neurological disease [ICD9: 338, 338.2, 410, 782.3,780; ICD10: I21, I22, R52, R52.1-R52.2, R60.9, G89]
Neuropathic pain [ICD9: 356.0, 356.8; ICD10: G64, G90.0]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
Spinal anesthesia [ICD9: 338; ICD10: R20.0]
Function
Tetrodotoxin-resistant channel that 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 sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.
BioChemical Class
Sodium channel
Target Validation
T43739
UniProt ID
Q9Y5Y9
Sequence
MEFPIGSLETNNFRRFTPESLVEIEKQIAAKQGTKKAREKHREQKDQEEKPRPQLDLKAC
NQLPKFYGELPAELIGEPLEDLDPFYSTHRTFMVLNKGRTISRFSATRALWLFSPFNLIR
RTAIKVSVHSWFSLFITVTILVNCVCMTRTDLPEKIEYVFTVIYTFEALIKILARGFCLN
EFTYLRDPWNWLDFSVITLAYVGTAIDLRGISGLRTFRVLRALKTVSVIPGLKVIVGALI
HSVKKLADVTILTIFCLSVFALVGLQLFKGNLKNKCVKNDMAVNETTNYSSHRKPDIYIN
KRGTSDPLLCGNGSDSGHCPDGYICLKTSDNPDFNYTSFDSFAWAFLSLFRLMTQDSWER
LYQQTLRTSGKIYMIFFVLVIFLGSFYLVNLILAVVTMAYEEQNQATTDEIEAKEKKFQE
ALEMLRKEQEVLAALGIDTTSLHSHNGSPLTSKNASERRHRIKPRVSEGSTEDNKSPRSD
PYNQRRMSFLGLASGKRRASHGSVFHFRSPGRDISLPEGVTDDGVFPGDHESHRGSLLLG
GGAGQQGPLPRSPLPQPSNPDSRHGEDEHQPPPTSELAPGAVDVSAFDAGQKKTFLSAEY
LDEPFRAQRAMSVVSIITSVLEELEESEQKCPPCLTSLSQKYLIWDCCPMWVKLKTILFG
LVTDPFAELTITLCIVVNTIFMAMEHHGMSPTFEAMLQIGNIVFTIFFTAEMVFKIIAFD
PYYYFQKKWNIFDCIIVTVSLLELGVAKKGSLSVLRSFRLLRVFKLAKSWPTLNTLIKII
GNSVGALGNLTIILAIIVFVFALVGKQLLGENYRNNRKNISAPHEDWPRWHMHDFFHSFL
IVFRILCGEWIENMWACMEVGQKSICLILFLTVMVLGNLVVLNLFIALLLNSFSADNLTA
PEDDGEVNNLQVALARIQVFGHRTKQALCSFFSRSCPFPQPKAEPELVVKLPLSSSKAEN
HIAANTARGSSGGLQAPRGPRDEHSDFIANPTVWVSVPIAEGESDLDDLEDDGGEDAQSF
QQEVIPKGQQEQLQQVERCGDHLTPRSPGTGTSSEDLAPSLGETWKDESVPQVPAEGVDD
TSSSEGSTVDCLDPEEILRKIPELADDLEEPDDCFTEGCIRHCPCCKLDTTKSPWDVGWQ
VRKTCYRIVEHSWFESFIIFMILLSSGSLAFEDYYLDQKPTVKALLEYTDRVFTFIFVFE
MLLKWVAYGFKKYFTNAWCWLDFLIVNISLISLTAKILEYSEVAPIKALRTLRALRPLRA
LSRFEGMRVVVDALVGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFWRCINYTDGEFSL
VPLSIVNNKSDCKIQNSTGSFFWVNVKVNFDNVAMGYLALLQVATFKGWMDIMYAAVDSR
EVNMQPKWEDNVYMYLYFVIFIIFGGFFTLNLFVGVIIDNFNQQKKKLGGQDIFMTEEQK
KYYNAMKKLGSKKPQKPIPRPLNKFQGFVFDIVTRQAFDITIMVLICLNMITMMVETDDQ
SEEKTKILGKINQFFVAVFTGECVMKMFALRQYYFTNGWNVFDFIVVVLSIASLIFSAIL
KSLQSYFSPTLFRVIRLARIGRILRLIRAAKGIRTLLFALMMSLPALFNIGLLLFLVMFI
YSIFGMSSFPHVRWEAGIDDMFNFQTFANSMLCLFQITTSAGWDGLLSPILNTGPPYCDP
NLPNSNGTRGDCGSPAVGIIFFTTYIIISFLIMVNMYIAVILENFNVATEESTEPLSEDD
FDMFYETWEKFDPEATQFITFSALSDFADTLSGPLRIPKPNRNILIQMDLPLVPGDKIHC
LDILFAFTKNVLGESGELDSLKANMEEKFMATNLSKSSYEPIATTLRWKQEDISATVIQK
AYRSYVLHRSMALSNTPCVPRAEEEAASLPDEGFVAFTANENCVLPDKSETASATSFPPS
YESVTRGLSDRVNMRTSSSIQNEDEATSMELIAPGP
Structure
1BYY
Drugs and Mode of Action
Drug(s) Bupivacaine Drug Info Approved Anesthesia [538239], [539524]
Proparacaine Drug Info Approved Anesthesia [538162], [542303]
Ropivacaine Drug Info Approved Anesthesia [538331], [542591]
Tetracaine Drug Info Approved Spinal anesthesia [535622]
Tetracaine Drug Info Phase 2 Pain [551871]
PF-01247324 Drug Info Phase 1 Pain [543182]
SPI-860 Drug Info Phase 1 Neuropathic pain [536374]
Corus 1030 Drug Info Discontinued in Phase 2 Asthma [547604]
SIPATRIGINE Drug Info Discontinued in Phase 2 Neurological disease [545614]
Inhibitor 1-[5-(4-Chlorophenyl)-2-furoyl]piperazine Drug Info [529491]
5-(4-chlorophenyl)-N-(2-methylbenzyl)nicotinamide Drug Info [531169]
A-803467 Drug Info [536866]
BW-202W92 Drug Info [530055]
Mu O-conotoxin Drug Info [535930]
N-(2-chlorobenzyl)-5-(4-chlorophenyl)nicotinamide Drug Info [531169]
N-benzyl-5-(4-chlorophenyl)nicotinamide Drug Info [531169]
SCH-725737 Drug Info [529019]
SCH-725739 Drug Info [529019]
SIPATRIGINE Drug Info [530055]
SPI-860 Drug Info [536374]
Tetracaine Drug Info [535913]
Activator batrachotoxin Drug Info [527277]
veratridine Drug Info [529119]
Modulator Bupivacaine Drug Info [556264]
Corus 1030 Drug Info [527078]
Proparacaine Drug Info [556264]
Ropivacaine Drug Info [556264]
Blocker CR-4892 Drug Info [543885]
PF-01247324 Drug Info [544467]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
Reactome Interaction between L1 and Ankyrins
References
Ref 535622Evaluation of a novel topical anesthetic agent for cutaneous laser resurfacing: a randomized comparison study. Dermatol Surg. 2002 Nov;28(11):1004-6; discussion 1006.
Ref 536374Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
Ref 538162FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 040074.
Ref 538239FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 071810.
Ref 538331FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 078601.
Ref 539524(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. (Ligand id: 2397).
Ref 542303(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. (Ligand id: 7283).
Ref 542591(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. (Ligand id: 7602).
Ref 543182(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. (Ligand id: 8521).
Ref 545614Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003904)
Ref 547604Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017745)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 527078Differential 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. Epub 2004 May 17.
Ref 527277The poison Dart frog's batrachotoxin modulates Nav1.8. FEBS Lett. 2004 Nov 5;577(1-2):245-8.
Ref 529019Bioorg Med Chem Lett. 2007 Oct 15;17(20):5543-7. Epub 2007 Aug 16.Novel steroidal saponins, Sch 725737 and Sch 725739, from a marine starfish, Novodinia antillensis.
Ref 529119A comparison of the effects of veratridine on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in isolated rat dorsal root ganglion neurons. Pflugers Arch. 2008 Feb;455(5):929-38. Epub 2007 Oct 26.
Ref 529491Bioorg Med Chem. 2008 Jun 15;16(12):6379-86. Epub 2008 May 6.Discovery of potent furan piperazine sodium channel blockers for treatment of neuropathic pain.
Ref 530055J Med Chem. 2009 May 14;52(9):2694-707.Oxadiazolylindazole sodium channel modulators are neuroprotective toward hippocampal neurones.
Ref 531169Bioorg Med Chem Lett. 2010 Nov 15;20(22):6812-5. Epub 2010 Sep 18.Subtype-selective Na(v)1.8 sodium channel blockers: identification of potent, orally active nicotinamide derivatives.
Ref 535913Heterologous expression and functional analysis of rat Nav1.8 (SNS) voltage-gated sodium channels in the dorsal root ganglion neuroblastoma cell line ND7-23. Neuropharmacology. 2004 Mar;46(3):425-38.
Ref 535930Structures of muO-conotoxins from Conus marmoreus. I nhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian sensory neurons. J Biol Chem. 2004 Jun 11;279(24):25774-82. Epub 2004 Mar 24.
Ref 536374Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
Ref 536866Sensory neuron voltage-gated sodium channels as analgesic drug targets. Curr Opin Neurobiol. 2008 Aug;18(4):383-8.
Ref 543885(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: 585).
Ref 544467Oral Administration of PF-01247324, a Subtype-Selective Nav1.8 Blocker, Reverses Cerebellar Deficits in a Mouse Model of Multiple Sclerosis. PLoS One. 2015; 10(3): e0119067.
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

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