Target Information
| Target General Information | Top | |||||
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| Target ID |
T39716
(Former ID: TTDS00402)
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| Target Name |
Voltage-gated sodium channel alpha Nav1.5 (SCN5A)
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| Synonyms |
Voltage-gated sodium channel subunit alpha Nav1.5; Sodium channel protein type V subunit alpha; Sodium channel protein type 5 subunit alpha; Sodium channel protein cardiac muscle subunit alpha; HH1
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| Gene Name |
SCN5A
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 8 Target-related Diseases | + | ||||
| 1 | Bacterial infection [ICD-11: 1A00-1C4Z] | |||||
| 2 | Cardiac arrhythmia [ICD-11: BC9Z] | |||||
| 3 | Corneal disease [ICD-11: 9A76-9A78] | |||||
| 4 | Cough [ICD-11: MD12] | |||||
| 5 | Epilepsy/seizure [ICD-11: 8A61-8A6Z] | |||||
| 6 | Migraine [ICD-11: 8A80] | |||||
| 7 | Pain [ICD-11: MG30-MG3Z] | |||||
| 8 | Ventricular tachyarrhythmia [ICD-11: BC71] | |||||
| Function |
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-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels. This protein mediates the voltage-dependent sodium ion permeability of excitable membranes.
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| BioChemical Class |
Voltage-gated ion channel
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| UniProt ID | ||||||
| Sequence |
MANFLLPRGTSSFRRFTRESLAAIEKRMAEKQARGSTTLQESREGLPEEEAPRPQLDLQA
SKKLPDLYGNPPQELIGEPLEDLDPFYSTQKTFIVLNKGKTIFRFSATNALYVLSPFHPI RRAAVKILVHSLFNMLIMCTILTNCVFMAQHDPPPWTKYVEYTFTAIYTFESLVKILARG FCLHAFTFLRDPWNWLDFSVIIMAYTTEFVDLGNVSALRTFRVLRALKTISVISGLKTIV GALIQSVKKLADVMVLTVFCLSVFALIGLQLFMGNLRHKCVRNFTALNGTNGSVEADGLV WESLDLYLSDPENYLLKNGTSDVLLCGNSSDAGTCPEGYRCLKAGENPDHGYTSFDSFAW AFLALFRLMTQDCWERLYQQTLRSAGKIYMIFFMLVIFLGSFYLVNLILAVVAMAYEEQN QATIAETEEKEKRFQEAMEMLKKEHEALTIRGVDTVSRSSLEMSPLAPVNSHERRSKRRK RMSSGTEECGEDRLPKSDSEDGPRAMNHLSLTRGLSRTSMKPRSSRGSIFTFRRRDLGSE ADFADDENSTAGESESHHTSLLVPWPLRRTSAQGQPSPGTSAPGHALHGKKNSTVDCNGV VSLLGAGDPEATSPGSHLLRPVMLEHPPDTTTPSEEPGGPQMLTSQAPCVDGFEEPGARQ RALSAVSVLTSALEELEESRHKCPPCWNRLAQRYLIWECCPLWMSIKQGVKLVVMDPFTD LTITMCIVLNTLFMALEHYNMTSEFEEMLQVGNLVFTGIFTAEMTFKIIALDPYYYFQQG WNIFDSIIVILSLMELGLSRMSNLSVLRSFRLLRVFKLAKSWPTLNTLIKIIGNSVGALG NLTLVLAIIVFIFAVVGMQLFGKNYSELRDSDSGLLPRWHMMDFFHAFLIIFRILCGEWI ETMWDCMEVSGQSLCLLVFLLVMVIGNLVVLNLFLALLLSSFSADNLTAPDEDREMNNLQ LALARIQRGLRFVKRTTWDFCCGLLRQRPQKPAALAAQGQLPSCIATPYSPPPPETEKVP PTRKETRFEEGEQPGQGTPGDPEPVCVPIAVAESDTDDQEEDEENSLGTEEESSKQQESQ PVSGGPEAPPDSRTWSQVSATASSEAEASASQADWRQQWKAEPQAPGCGETPEDSCSEGS TADMTNTAELLEQIPDLGQDVKDPEDCFTEGCVRRCPCCAVDTTQAPGKVWWRLRKTCYH IVEHSWFETFIIFMILLSSGALAFEDIYLEERKTIKVLLEYADKMFTYVFVLEMLLKWVA YGFKKYFTNAWCWLDFLIVDVSLVSLVANTLGFAEMGPIKSLRTLRALRPLRALSRFEGM RVVVNALVGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFGRCINQTEGDLPLNYTIVNN KSQCESLNLTGELYWTKVKVNFDNVGAGYLALLQVATFKGWMDIMYAAVDSRGYEEQPQW EYNLYMYIYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAMKK LGSKKPQKPIPRPLNKYQGFIFDIVTKQAFDVTIMFLICLNMVTMMVETDDQSPEKINIL AKINLLFVAIFTGECIVKLAALRHYYFTNSWNIFDFVVVILSIVGTVLSDIIQKYFFSPT LFRVIRLARIGRILRLIRGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYSIFGMANFA YVKWEAGIDDMFNFQTFANSMLCLFQITTSAGWDGLLSPILNTGPPYCDPTLPNSNGSRG DCGSPAVGILFFTTYIIISFLIVVNMYIAIILENFSVATEESTEPLSEDDFDMFYEIWEK FDPEATQFIEYSVLSDFADALSEPLRIAKPNQISLINMDLPMVSGDRIHCMDILFAFTKR VLGESGEMDALKIQMEEKFMAANPSKISYEPITTTLRRKHEEVSAMVIQRAFRRHLLQRS LKHASFLFRQQAGSGLSEEDAPEREGLIAYVMSENFSRPLGPPSSSSISSTSFPPSYDSV TRATSDNLQVRGSDYSHSEDLADFPPSPDRDRESIV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| ADReCS ID | BADD_A04830 | |||||
| HIT2.0 ID | T77X36 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 14 Approved Drugs | + | ||||
| 1 | Benzonatate | Drug Info | Approved | Cough | [2], [3] | |
| 2 | Dibucaine | Drug Info | Approved | Anaesthesia | [4], [5], [6] | |
| 3 | Disopyramide | Drug Info | Approved | Ventricular arrhythmias | [7], [8] | |
| 4 | Dyclonine | Drug Info | Approved | Pain | [6], [9], [10] | |
| 5 | Ethotoin | Drug Info | Approved | Complex partial seizure | [11], [12] | |
| 6 | Fosphenytoin | Drug Info | Approved | Epilepsy | [6] | |
| 7 | Hexylcaine | Drug Info | Approved | Anaesthesia | [6] | |
| 8 | Indecainide | Drug Info | Approved | Dysrhythmias | [13] | |
| 9 | LOMERIZINE | Drug Info | Approved | Migraine | [6], [14] | |
| 10 | Mephenytoin | Drug Info | Approved | Epilepsy | [15], [16] | |
| 11 | Mexiletine | Drug Info | Approved | Ventricular tachycardia | [6] | |
| 12 | Moricizine | Drug Info | Approved | Arrhythmia | [6] | |
| 13 | Prilocaine | Drug Info | Approved | Pain | [6], [17], [18] | |
| 14 | Tetrodotoxin | Drug Info | Approved | Bacterial infection | [19], [20] | |
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | F-15845 | Drug Info | Phase 1 | Angina pectoris | [21] | |
| Discontinued Drug(s) | [+] 4 Discontinued Drugs | + | ||||
| 1 | Encainide | Drug Info | Withdrawn from market | Heart arrhythmia | [22], [6] | |
| 2 | LUBELUZOLE | Drug Info | Discontinued in Preregistration | Neurological disorder | [23] | |
| 3 | Acecainide | Drug Info | Discontinued in Phase 3 | Solid tumour/cancer | [24] | |
| 4 | SIPATRIGINE | Drug Info | Discontinued in Phase 2 | Neurological disorder | [25] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Blocker | [+] 16 Blocker drugs | + | ||||
| 1 | Benzonatate | Drug Info | [26] | |||
| 2 | Dibucaine | Drug Info | [20] | |||
| 3 | Disopyramide | Drug Info | [27] | |||
| 4 | Dyclonine | Drug Info | [28] | |||
| 5 | Ethotoin | Drug Info | [26] | |||
| 6 | Fosphenytoin | Drug Info | [29] | |||
| 7 | Hexylcaine | Drug Info | [26] | |||
| 8 | Indecainide | Drug Info | [1] | |||
| 9 | Mephenytoin | Drug Info | [29] | |||
| 10 | Mexiletine | Drug Info | [27] | |||
| 11 | Moricizine | Drug Info | [31] | |||
| 12 | Prilocaine | Drug Info | [28] | |||
| 13 | Tetrodotoxin | Drug Info | [20] | |||
| 14 | Dihydrobenzoxazine and tetrahydroquinoxaline sulfonamide derivative 1 | Drug Info | [34] | |||
| 15 | Encainide | Drug Info | [31] | |||
| 16 | Acecainide | Drug Info | [28] | |||
| Inhibitor | [+] 12 Inhibitor drugs | + | ||||
| 1 | LOMERIZINE | Drug Info | [30] | |||
| 2 | F-15845 | Drug Info | [32], [33] | |||
| 3 | Aryl carboxamide derivative 1 | Drug Info | [34] | |||
| 4 | Aryl carboxamide derivative 2 | Drug Info | [34] | |||
| 5 | Aryl carboxamide derivative 3 | Drug Info | [34] | |||
| 6 | LUBELUZOLE | Drug Info | [30] | |||
| 7 | SIPATRIGINE | Drug Info | [30] | |||
| 8 | PD-85639 | Drug Info | [30] | |||
| 9 | 1-[5-(4-Chlorophenyl)-2-furoyl]piperazine | Drug Info | [35] | |||
| 10 | KC-12291 | Drug Info | [38] | |||
| 11 | N-(4-Methyl-benzoyl)-N'-phenethyl-guanidine | Drug Info | [39] | |||
| 12 | N-Butyl-N'-(4-methyl-benzoyl)-guanidine | Drug Info | [39] | |||
| Activator | [+] 3 Activator drugs | + | ||||
| 1 | aconitine | Drug Info | [36] | |||
| 2 | batrachotoxin | Drug Info | [37] | |||
| 3 | veratridine | Drug Info | [40] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Adrenergic signaling in cardiomyocytes | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Muscle/Heart Contraction | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Interaction between L1 and Ankyrins | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | SIDS Susceptibility Pathways | |||||
| 2 | Cardiac Progenitor Differentiation | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Electrophysiological studies of indecainide hydrochloride, a new antiarrhythmic agent, in canine cardiac tissues. J Cardiovasc Pharmacol. 1984 Jul-Aug;6(4):614-21. | |||||
| REF 2 | 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. (Ligand id: 7611). | |||||
| REF 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 040587. | |||||
| REF 4 | 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. (Ligand id: 7159). | |||||
| REF 5 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 006203. | |||||
| REF 6 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 7 | 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. (Ligand id: 7167). | |||||
| REF 8 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 070101. | |||||
| REF 9 | 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. (Ligand id: 7173). | |||||
| REF 10 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 009925. | |||||
| REF 11 | 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. (Ligand id: 7183). | |||||
| REF 12 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 010841. | |||||
| REF 13 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019693. | |||||
| REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002033) | |||||
| REF 15 | 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. (Ligand id: 7223). | |||||
| REF 16 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 006008. | |||||
| REF 17 | 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. (Ligand id: 7276). | |||||
| REF 18 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 076290. | |||||
| REF 19 | 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. (Ligand id: 2616). | |||||
| REF 20 | Halothane attenuates the cerebroprotective action of several Na+ and Ca2+ channel blockers via reversal of their ion channel blockade. Eur J Pharmacol. 2002 Oct 4;452(2):175-81. | |||||
| REF 21 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023448) | |||||
| REF 22 | New antiarrhythmic drugs: tocainide, mexiletine, flecainide, encainide, and amiodarone. Mayo Clin Proc. 1987 Nov;62(11):1033-50. | |||||
| REF 23 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005388) | |||||
| REF 24 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000315) | |||||
| REF 25 | 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 26 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 27 | Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome. J Cardiovasc Electrophysiol. 2000 Dec;11(12):1320-9. | |||||
| REF 28 | Monoamine transporter and sodium channel mechanisms in the rapid pressor response to cocaine. Pharmacol Biochem Behav. 1998 Feb;59(2):305-12. | |||||
| REF 29 | Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders. CNS Drugs. 2009;23(7):555-68. | |||||
| REF 30 | Medicinal chemistry of neuronal voltage-gated sodium channel blockers. J Med Chem. 2001 Jan 18;44(2):115-37. | |||||
| REF 31 | From first class to third class: recent upheaval in antiarrhythmic therapy--lessons from clinical trials. Am J Cardiol. 1996 Aug 29;78(4A):28-33. | |||||
| REF 32 | Selective inhibition of persistent sodium current by F 15845 prevents ischaemia-induced arrhythmias. Br J Pharmacol. 2010 Sep;161(1):79-91. | |||||
| REF 33 | A rare loss-of-function SCN5A variant is associated with lidocaine-induced ventricular fibrillation. Pharmacogenomics J. 2014 Aug;14(4):372-5. | |||||
| REF 34 | Sodium channel blockers: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015 Mar;25(3):279-90. | |||||
| REF 35 | Discovery of potent furan piperazine sodium channel blockers for treatment of neuropathic pain. Bioorg Med Chem. 2008 Jun 15;16(12):6379-86. | |||||
| REF 36 | Properties of aconitine-modified sodium channels in single cells of mouse ventricular myocardium. Gen Physiol Biophys. 1986 Oct;5(5):473-84. | |||||
| REF 37 | Binding of [3H]batrachotoxinin A benzoate to specific sites on rat cardiac sodium channels. Mol Pharmacol. 1986 Dec;30(6):617-23. | |||||
| REF 38 | Sodium late current blockers in ischemia reperfusion: is the bullet magic J Med Chem. 2008 Jul 10;51(13):3856-66. | |||||
| REF 39 | Solution-phase, parallel synthesis and pharmacological evaluation of acylguanidine derivatives as potential sodium channel blockers. Bioorg Med Chem Lett. 2001 Dec 17;11(24):3151-5. | |||||
| REF 40 | Sodium channel comodification with full activator reveals veratridine reaction dynamics. Mol Pharmacol. 1990 Feb;37(2):144-8. | |||||
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