Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T43739
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| Former ID |
TTDS00514
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| Target Name |
Voltage-gated sodium channel subunit alpha Nav1.8
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| Gene Name |
SCN10A
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| Synonyms |
PN3; SNS; TTX-R sodium channel; TTX-R/NaV1.8; Transient tetrodotoxin-resistant Na+ current; Voltage-gated sodium channel NaV1.8; SCN10A
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| Target Type |
Successful
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| Disease | Asthma [ICD10: J45] | ||||
| Anesthesia [ICD9: 338; ICD10: R20.0] | |||||
| Neuropathic pain [ICD9: 356.0, 356.8; ICD10: G64, G90.0] | |||||
| Neurological disease [ICD9: 338, 338.2, 410, 782.3,780; ICD10: I21, I22, R52, R52.1-R52.2, R60.9, G89] | |||||
| 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.
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| BioChemical Class |
Sodium channel
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| Target Validation |
T43739
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| UniProt ID | |||||
| 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 |
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| Structure |
1BYY
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| Drugs and Mode of Action | |||||
| Drug(s) | Bupivacaine | Drug Info | Approved | Anesthesia | [1], [2] |
| Proparacaine | Drug Info | Approved | Anesthesia | [3], [4] | |
| Ropivacaine | Drug Info | Approved | Anesthesia | [5], [6] | |
| Tetracaine | Drug Info | Approved | Spinal anesthesia | [7] | |
| Tetracaine | Drug Info | Phase 2 | Pain | [8] | |
| PF-01247324 | Drug Info | Phase 1 | Pain | [9] | |
| SPI-860 | Drug Info | Phase 1 | Neuropathic pain | [10] | |
| Corus 1030 | Drug Info | Discontinued in Phase 2 | Asthma | [11] | |
| SIPATRIGINE | Drug Info | Discontinued in Phase 2 | Neurological disease | [12] | |
| Inhibitor | 1-[5-(4-Chlorophenyl)-2-furoyl]piperazine | Drug Info | [13] | ||
| 5-(4-chlorophenyl)-N-(2-methylbenzyl)nicotinamide | Drug Info | [14] | |||
| A-803467 | Drug Info | [15] | |||
| BW-202W92 | Drug Info | [16] | |||
| Mu O-conotoxin | Drug Info | [17] | |||
| N-(2-chlorobenzyl)-5-(4-chlorophenyl)nicotinamide | Drug Info | [14] | |||
| N-benzyl-5-(4-chlorophenyl)nicotinamide | Drug Info | [14] | |||
| SCH-725737 | Drug Info | [18] | |||
| SCH-725739 | Drug Info | [18] | |||
| SIPATRIGINE | Drug Info | [16] | |||
| SPI-860 | Drug Info | [10] | |||
| Tetracaine | Drug Info | [19] | |||
| Activator | batrachotoxin | Drug Info | [20] | ||
| veratridine | Drug Info | [21] | |||
| Modulator | Bupivacaine | Drug Info | [22] | ||
| Corus 1030 | Drug Info | [23] | |||
| Proparacaine | Drug Info | [22] | |||
| Ropivacaine | Drug Info | [22] | |||
| Blocker | CR-4892 | Drug Info | [24] | ||
| PF-01247324 | Drug Info | [25] | |||
| Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
| TEP | EXP Info | ||||
| Pathways | |||||
| Reactome | Interaction between L1 and Ankyrins | ||||
| References | |||||
| REF 1 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 071810. | ||||
| REF 2 | (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 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 040074. | ||||
| REF 4 | (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 5 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 078601. | ||||
| REF 6 | (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 7 | Evaluation 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 8 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | ||||
| REF 9 | (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 10 | Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26. | ||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017745) | ||||
| REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003904) | ||||
| REF 13 | Bioorg 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 14 | Bioorg 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 15 | Sensory neuron voltage-gated sodium channels as analgesic drug targets. Curr Opin Neurobiol. 2008 Aug;18(4):383-8. | ||||
| REF 16 | J Med Chem. 2009 May 14;52(9):2694-707.Oxadiazolylindazole sodium channel modulators are neuroprotective toward hippocampal neurones. | ||||
| REF 17 | Structures 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 18 | Bioorg 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 19 | Heterologous 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 20 | The poison Dart frog's batrachotoxin modulates Nav1.8. FEBS Lett. 2004 Nov 5;577(1-2):245-8. | ||||
| REF 21 | A 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 22 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | ||||
| REF 23 | 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. Epub 2004 May 17. | ||||
| REF 24 | (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 25 | Oral 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. | ||||
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