Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTWK8D0)

• DTT Name: Sodium pump subunit alpha-1 (ATP1A1)
• Synonyms: Sodium/potassium-transporting ATPase alpha1; Sodium pump 1; Na+/K+ ATPase 1; ATP1A1
• Gene Name: ATP1A1
• DTT Type: Successful target; [1]
• Related Disease:
  Cardiac arrhythmia [ICD-11: BC9Z]
  Chronic obstructive pulmonary disease [ICD-11: CA22]
  Corneal disease [ICD-11: 9A76-9A78]
  Heart failure [ICD-11: BD10-BD1Z]
  Hyperhidrosis [ICD-11: EE00]
  Malaria [ICD-11: 1F40-1F45]
  Supraventricular tachyarrhythmia [ICD-11: BC81]
• BioChemical Class: Acid anhydrides hydrolase
• UniProt ID: AT1A1_HUMAN
• TTD ID: T40800
• EC Number: EC 7.2.2.13
• Sequence:
  MGKGVGRDKYEPAAVSEQGDKKGKKGKKDRDMDELKKEVSMDDHKLSLDELHRKYGTDLS
  RGLTSARAAEILARDGPNALTPPPTTPEWIKFCRQLFGGFSMLLWIGAILCFLAYSIQAA
  TEEEPQNDNLYLGVVLSAVVIITGCFSYYQEAKSSKIMESFKNMVPQQALVIRNGEKMSI
  NAEEVVVGDLVEVKGGDRIPADLRIISANGCKVDNSSLTGESEPQTRSPDFTNENPLETR
  NIAFFSTNCVEGTARGIVVYTGDRTVMGRIATLASGLEGGQTPIAAEIEHFIHIITGVAV
  FLGVSFFILSLILEYTWLEAVIFLIGIIVANVPEGLLATVTVCLTLTAKRMARKNCLVKN
  LEAVETLGSTSTICSDKTGTLTQNRMTVAHMWFDNQIHEADTTENQSGVSFDKTSATWLA
  LSRIAGLCNRAVFQANQENLPILKRAVAGDASESALLKCIELCCGSVKEMRERYAKIVEI
  PFNSTNKYQLSIHKNPNTSEPQHLLVMKGAPERILDRCSSILLHGKEQPLDEELKDAFQN
  AYLELGGLGERVLGFCHLFLPDEQFPEGFQFDTDDVNFPIDNLCFVGLISMIDPPRAAVP
  DAVGKCRSAGIKVIMVTGDHPITAKAIAKGVGIISEGNETVEDIAARLNIPVSQVNPRDA
  KACVVHGSDLKDMTSEQLDDILKYHTEIVFARTSPQQKLIIVEGCQRQGAIVAVTGDGVN
  DSPALKKADIGVAMGIAGSDVSKQAADMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTL
  TSNIPEITPFLIFIIANIPLPLGTVTILCIDLGTDMVPAISLAYEQAESDIMKRQPRNPK
  TDKLVNERLISMAYGQIGMIQALGGFFTYFVILAENGFLPIHLLGLRVDWDDRWINDVED
  SYGQQWTYEQRKIVEFTCHTAFFVSIVVVQWADLVICKTRRNSVFQQGMKNKILIFGLFE
  ETALAAFLSYCPGMGVALRMYPLKPTWWFCAFPYSLLIFVYDEVRKLIIRRRPGGWVEKE
  TYY
• Function: This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of atp coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions.
• KEGG Pathway:
  cGMP-PKG signaling pathway (hsa04022)
  cAMP signaling pathway (hsa04024)
  Cardiac muscle contraction (hsa04260)
  Adrenergic signaling in cardiomyocytes (hsa04261)
  Insulin secretion (hsa04911)
  Thyroid hormone synthesis (hsa04918)
  Thyroid hormone signaling pathway (hsa04919)
  Aldosterone-regulated sodium reabsorption (hsa04960)
  Endocrine and other factor-regulated calcium reabsorption (hsa04961)
  Proximal tubule bicarbonate reclamation (hsa04964)
  Salivary secretion (hsa04970)
  Gastric acid secretion (hsa04971)
  Pancreatic secretion (hsa04972)
  Carbohydrate digestion and absorption (hsa04973)
  Protein digestion and absorption (hsa04974)
  Bile secretion (hsa04976)
  Mineral absorption (hsa04978)
• Reactome Pathway: Ion transport by P-type ATPases (R-HSA-936837)

Molecular Interaction Atlas (MIA) of This DTT

8 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetyldigitoxin	DMHAUO0	Congestive heart failure	BD10	Approved	[2]
Acocantherin	DM7JT24	Atrial fibrillation	BC81.3	Approved	[1]
Almitrine	DM0SYAN	Chronic obstructive pulmonary disease	CA22	Approved	[3], [4]
Aluminium	DM6ECN9	Hyperhidrosis	EE00	Approved	[5], [6]
Artemether	DM48QOT	Malaria	1F40-1F45	Approved	[7]
Chloroprocaine	DMSOQK1	Anaesthesia	9A78.6	Approved	[8]
Deslanoside	DMB3ZSK	Arrhythmia	BC9Z	Approved	[1]
Lumefantrine	DM29GAD	Malaria	1F40-1F45	Approved	[7]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
UNBS-1450	DMR38M4	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Digitoxigenin	DM5AOFW	Discovery agent	N.A.	Investigative	[10]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Chronic obstructive pulmonary disease	CA23	Lung tissue	4.66E-01	1.00E-02	0.06
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	3.31E-01	-0.03	-0.19

References

• [1] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [3] Almitrine, a new kind of energy-transduction inhibitor acting on mitochondrial ATP synthase. Biochim Biophys Acta. 1989 Aug 3;975(3):325-9.
• [4] Flux-dependent increase in the stoichiometry of charge translocation by mitochondrial ATPase/ATP synthase induced by almitrine. Biochim Biophys Acta. 1990 Jul 17;1018(1):91-7.
• [5] The inhibitory effect of aluminium on the (Na+/K+)ATPase activity of rat brain cortex synaptosomes. J Inorg Biochem. 2003 Sep 15;97(1):143-50.
• [6] Effects of aluminium and lead on ATPase activity of knockout +/- mouse cerebral synaptosomes in vitro. Altern Lab Anim. 2004 Oct;32(4):361-7.
• [7] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [8] Inhibition of the Na,K-ATPase of canine renal medulla by several local anesthetics. Pharmacol Res. 2001 Apr;43(4):399-403.
• [9] Early downregulation of Mcl-1 regulates apoptosis triggered by cardiac glycoside UNBS1450. Cell Death Dis. 2015 Jun 11;6:e1782.
• [10] 17beta-O-Aminoalkyloximes of 5beta-androstane-3beta,14beta-diol with digitalis-like activity: synthesis, cardiotonic activity, structure-activity r... J Med Chem. 2000 Jun 15;43(12):2332-49.