Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQM7TE)

• DTT Name: Amiloride-sensitive sodium channel (ENaC)
• Synonyms: SCNE; Nonvoltage-gated sodium channel 1; NaCH; Epithelial Na(+) channel; ENaC
• Gene Name: SCNN1A
• DTT Type: Successful target; [1]
• BioChemical Class: Epithelial sodium channel
• UniProt ID: SCNNA_HUMAN ; SCNNB_HUMAN ; SCNNG_HUMAN ; SCNND_HUMAN
• TTD ID: T52173
• Sequence:
  MEGNKLEEQDSSPPQSTPGLMKGNKREEQGLGPEPAAPQQPTAEEEALIEFHRSYRELFE
  FFCNNTTIHGAIRLVCSQHNRMKTAFWAVLWLCTFGMMYWQFGLLFGEYFSYPVSLNINL
  NSDKLVFPAVTICTLNPYRYPEIKEELEELDRITEQTLFDLYKYSSFTTLVAGSRSRRDL
  RGTLPHPLQRLRVPPPPHGARRARSVASSLRDNNPQVDWKDWKIGFQLCNQNKSDCFYQT
  YSSGVDAVREWYRFHYINILSRLPETLPSLEEDTLGNFIFACRFNQVSCNQANYSHFHHP
  MYGNCYTFNDKNNSNLWMSSMPGINNGLSLMLRAEQNDFIPLLSTVTGARVMVHGQDEPA
  FMDDGGFNLRPGVETSISMRKETLDRLGGDYGDCTKNGSDVPVENLYPSKYTQQVCIHSC
  FQESMIKECGCAYIFYPRPQNVEYCDYRKHSSWGYCYYKLQVDFSSDHLGCFTKCRKPCS
  VTSYQLSAGYSRWPSVTSQEWVFQMLSRQNNYTVNNKRNGVAKVNIFFKELNYKTNSESP
  SVTMVTLLSNLGSQWSLWFGSSVLSVVEMAELVFDLLVIMFLMLLRRFRSRYWSPGRGGR
  GAQEVASTLASSPPSHFCPHPMSLSLSQPGPAPSPALTAPPPAYATLGPRPSPGGSAGAS
  SSTCPLGGP
• 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.
• KEGG Pathway:
  Taste transduction (hsa04742)
  Aldosterone-regulated sodium reabsorption (hsa04960)
• Reactome Pathway: Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Triamterene	DM2HU9I	Congestive heart failure	BD10	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VX-371	DMSTHG1	Cystic fibrosis	CA25	Phase 2	[2]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
benzamil	DM57SVW	Discovery agent	N.A.	Investigative	[3]
S3969	DM84DMW	Discovery agent	N.A.	Investigative	[4]

References

• [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.
• [2] The in vitro effect of nebulised hypertonic saline on human bronchial epithelium. Eur Respir J. 2018 May 17;51(5):1702652.
• [3] 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).
• [4] Small molecule activator of the human epithelial sodium channel. J Biol Chem. 2008 May 2;283(18):11981-94.