Target Information

Target General Infomation
Target ID
T12119
Former ID
TTDS00503
Target Name
Voltage-gated sodium channel subunit alpha Nav1.7
Gene Name
SCN9A
Synonyms
Neuroendocrine sodium channel; Peripheral sodium channel 1; Sodium channel proteintype 9 subunit alpha; Sodium channel proteintype IX subunit alpha; hNE-Na; SCN9A
Target Type
Clinical Trial
Disease Asthma [ICD10: J45]
Chronic pain [ICD9: 338.2,780; ICD10: R52.1-R52.2, G89]
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]
Function
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 channelthrough which na+ ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive na+ channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain.
BioChemical Class
Voltage-gated ion channel
Target Validation
T12119
UniProt ID
Q15858
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
Drugs and Mode of Action
Drug(s) PF-05089771 Drug Info Phase 2 Chronic pain [1]
XEN-402 Drug Info Phase 2 Pain [2]
PF-05186462 Drug Info Phase 1 Pain [3]
PF-05241328 Drug Info Phase 1 Pain [3]
RG7893 Drug Info Phase 1 Pain [4]
Corus 1030 Drug Info Discontinued in Phase 2 Asthma [5]
SIPATRIGINE Drug Info Discontinued in Phase 2 Neurological disease [6]
V-102862 Drug Info Discontinued in Phase 1 Discovery agent [7]
Inhibitor 4-(2'-(trifluoromethoxy)biphenyl-3-yl)oxazole Drug Info [8]
4-(2'-(trifluoromethoxy)biphenyl-3-yl)thiazole Drug Info [8]
4-(2'-(trifluoromethyl)biphenyl-3-yl)oxazole Drug Info [8]
PF-05186462 Drug Info [9]
PF-05241328 Drug Info [10]
RG7893 Drug Info [11], [12]
SIPATRIGINE Drug Info [13]
V-102862 Drug Info [8]
XEN-402 Drug Info [14]
XEN-907 Drug Info [15]
Activator batrachotoxin Drug Info [15]
veratridine Drug Info [15]
Modulator Corus 1030 Drug Info [16]
Inhibitor (gating inhibitor) N-Me-aminopyrimidinone 9 Drug Info [17]
Blocker PF-05089771 Drug Info [18]
Blocker (channel blocker) pyrrolopyrimidine 48 Drug Info [19]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
DRM DRM Info
Pathways
Reactome Interaction between L1 and Ankyrins
References
REF 1ClinicalTrials.gov (NCT01529346) Efficacy Of PF-05089771 In Treating Postoperative Dental Pain. U.S. National Institutes of Health.
REF 2ClinicalTrials.gov (NCT01195636) A Crossover Study to Evaluate the Safety, Tolerability and Efficacy of XPF-002 in Subjects With Postherpetic Neuralgia (PHN). U.S. National Institutes of Health.
REF 3ClinicalTrials.gov (NCT01165736) To Calculate the Pharmacokinetics (Concentration of Compound in and Rate of Excretion From the Blood) Following a Very Low Dose of Compound Which Will Not Have Any Pharmacological Activity. U.S. National Institutes of Health.
REF 4Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800041740)
REF 5Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017745)
REF 6Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003904)
REF 7Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009655)
REF 8Bioorg Med Chem Lett. 2010 Sep 15;20(18):5536-40. Epub 2010 Jul 21.Substituted biaryl oxazoles, imidazoles, and thiazoles as sodium channel blockers.
REF 9Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026875)
REF 10Recent progress in sodium channel modulators for pain. Bioorg Med Chem Lett. 2014 Aug 15;24(16):3690-9.
REF 11Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800041740)
REF 12Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 13J Med Chem. 2009 May 14;52(9):2694-707.Oxadiazolylindazole sodium channel modulators are neuroprotective toward hippocampal neurones.
REF 14Treatment of Na(v)1.7-mediated pain in inherited erythromelalgia using a novel sodium channel blocker. Pain. 2012 Jan;153(1):80-5.
REF 15(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).
REF 16Differential 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 17Discovery and optimization of aminopyrimidinones as potent and state-dependent Nav1.7 antagonists. Bioorg Med Chem Lett. 2012 Jan 15;22(2):1055-60.
REF 18Primary erythromelalgia: a review. Orphanet J Rare Dis. 2015 Sep 30;10:127.
REF 19Discovery 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.

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