Target Information
| Target General Information | Top | |||||
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| Target ID |
T52173
(Former ID: TTDS00158)
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| Target Name |
Amiloride-sensitive sodium channel (ENaC)
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| Synonyms |
SCNE; Nonvoltage-gated sodium channel 1; NaCH; Epithelial Na(+) channel; ENaC
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| Gene Name |
SCNN1A; SCNN1B; SCNN1G; SCNN1D
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Heart failure [ICD-11: BD10-BD1Z] | |||||
| 2 | Hypertension [ICD-11: BA00-BA04] | |||||
| 3 | Oedema [ICD-11: MG29] | |||||
| Function |
Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption ofsodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception.
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| BioChemical Class |
Epithelial sodium channel
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| UniProt ID | ||||||
| Sequence |
MEGNKLEEQDSSPPQSTPGLMKGNKREEQGLGPEPAAPQQPTAEEEALIEFHRSYRELFE
FFCNNTTIHGAIRLVCSQHNRMKTAFWAVLWLCTFGMMYWQFGLLFGEYFSYPVSLNINL NSDKLVFPAVTICTLNPYRYPEIKEELEELDRITEQTLFDLYKYSSFTTLVAGSRSRRDL RGTLPHPLQRLRVPPPPHGARRARSVASSLRDNNPQVDWKDWKIGFQLCNQNKSDCFYQT YSSGVDAVREWYRFHYINILSRLPETLPSLEEDTLGNFIFACRFNQVSCNQANYSHFHHP MYGNCYTFNDKNNSNLWMSSMPGINNGLSLMLRAEQNDFIPLLSTVTGARVMVHGQDEPA FMDDGGFNLRPGVETSISMRKETLDRLGGDYGDCTKNGSDVPVENLYPSKYTQQVCIHSC FQESMIKECGCAYIFYPRPQNVEYCDYRKHSSWGYCYYKLQVDFSSDHLGCFTKCRKPCS VTSYQLSAGYSRWPSVTSQEWVFQMLSRQNNYTVNNKRNGVAKVNIFFKELNYKTNSESP SVTMVTLLSNLGSQWSLWFGSSVLSVVEMAELVFDLLVIMFLMLLRRFRSRYWSPGRGGR GAQEVASTLASSPPSHFCPHPMSLSLSQPGPAPSPALTAPPPAYATLGPRPSPGGSAGAS SSTCPLGGP Click to Show/Hide
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| HIT2.0 ID | T02YDU ; T08Q1T ; T18DZZ | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Triamterene | Drug Info | Approved | Congestive heart failure | [2], [3], [4] | |
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | VX-371 | Drug Info | Phase 2 | Cystic fibrosis | [5] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Blocker | [+] 1 Blocker drugs | + | ||||
| 1 | Triamterene | Drug Info | [1] | |||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | VX-371 | Drug Info | [6] | |||
| Blocker (channel blocker) | [+] 1 Blocker (channel blocker) drugs | + | ||||
| 1 | benzamil | Drug Info | [7] | |||
| Activator | [+] 1 Activator drugs | + | ||||
| 1 | S3969 | Drug Info | [8] | |||
| 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 | ||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Taste transduction | |||||
| 2 | Aldosterone-regulated sodium reabsorption | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Kidney Function | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Stimuli-sensing channels | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | Nuclear Receptors Meta-Pathway | |||||
| 2 | Iron uptake and transport | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Effects of the serine/threonine kinase SGK1 on the epithelial Na(+) channel (ENaC) and CFTR: implications for cystic fibrosis. Cell Physiol Biochem. 2001;11(4):209-18. | |||||
| 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: 4329). | |||||
| REF 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 071251. | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 5 | ClinicalTrials.gov (NCT02709109) A Study to Evaluate the Safety and Efficacy of VX-371 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation. U.S. National Institutes of Health. | |||||
| REF 6 | The in vitro effect of nebulised hypertonic saline on human bronchial epithelium. Eur Respir J. 2018 May 17;51(5):1702652. | |||||
| 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. (Target id: 742). | |||||
| REF 8 | Small molecule activator of the human epithelial sodium channel. J Biol Chem. 2008 May 2;283(18):11981-94. | |||||
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