Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQ38E9)

• DTT Name: Sodium/potassium-transporting ATPase (SPT ATPase)
• Synonyms: Na(+)/K(+) ATPase
• Gene Name: ATP1A1
• DTT Type: Successful target; [1]
• BioChemical Class: Acid anhydrides hydrolase
• UniProt ID: AT1A1_HUMAN ; AT1A2_HUMAN ; AT1A3_HUMAN ; AT1B1_HUMAN ; AT1B2_HUMAN ; AT1B3_HUMAN
• TTD ID: T03917
• Sequence:
  MGKGVGRDKYEPAAVSEQGDKKGKKGKKDRDMDELKKEVSMDDHKLSLDELHRKYGTDLS
  RGLTSARAAEILARDGPNALTPPPTTPEWIKFCRQLFGGFSMLLWIGAILCFLAYSIQAA
  TEEEPQNDNLYLGVVLSAVVIITGCFSYYQEAKSSKIMESFKNMVPQQALVIRNGEKMSI
  NAEEVVVGDLVEVKGGDRIPADLRIISANGCKVDNSSLTGESEPQTRSPDFTNENPLETR
  NIAFFSTNCVEGTARGIVVYTGDRTVMGRIATLASGLEGGQTPIAAEIEHFIHIITGVAV
  FLGVSFFILSLILEYTWLEAVIFLIGIIVANVPEGLLATVTVCLTLTAKRMARKNCLVKN
  LEAVETLGSTSTICSDKTGTLTQNRMTVAHMWFDNQIHEADTTENQSGVSFDKTSATWLA
  LSRIAGLCNRAVFQANQENLPILKRAVAGDASESALLKCIELCCGSVKEMRERYAKIVEI
  PFNSTNKYQLSIHKNPNTSEPQHLLVMKGAPERILDRCSSILLHGKEQPLDEELKDAFQN
  AYLELGGLGERVLGFCHLFLPDEQFPEGFQFDTDDVNFPIDNLCFVGLISMIDPPRAAVP
  DAVGKCRSAGIKVIMVTGDHPITAKAIAKGVGIISEGNETVEDIAARLNIPVSQVNPRDA
  KACVVHGSDLKDMTSEQLDDILKYHTEIVFARTSPQQKLIIVEGCQRQGAIVAVTGDGVN
  DSPALKKADIGVAMGIAGSDVSKQAADMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTL
  TSNIPEITPFLIFIIANIPLPLGTVTILCIDLGTDMVPAISLAYEQAESDIMKRQPRNPK
  TDKLVNERLISMAYGQIGMIQALGGFFTYFVILAENGFLPIHLLGLRVDWDDRWINDVED
  SYGQQWTYEQRKIVEFTCHTAFFVSIVVVQWADLVICKTRRNSVFQQGMKNKILIFGLFE
  ETALAAFLSYCPGMGVALRMYPLKPTWWFCAFPYSLLIFVYDEVRKLIIRRRPGGWVEKE
  TYY
• Function: Maintain resting potential, affects transport, and regulates cellular volume. Function as a signal transducer/integrator to regulate the MAPK pathway, ROS, as well as intracellular calcium.
• 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)
  Potential therapeutics for SARS (R-HSA-9679191)
  Ion homeostasis (R-HSA-5578775)

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Digitoxin	DMWVIGP	Arrhythmia	BC9Z	Approved	[1]
Digoxin	DMQCTIH	Arrhythmia	BC9Z	Approved	[2]
Sanguinarine	DMDINFS	Dental plaque	DA08.4	Approved	[3]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PBI-05204	DM05WIU	Pancreatic cancer	2C10	Phase 2	[4]
Rostafuroxin	DMKQXDB	Hypertension	BA00-BA04	Phase 2	[5]
RX108	DM4XETK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Istaroxime	DMWN09H	Cardiac disease	BA00-BE2Z	Discontinued in Phase 2	[7]
Cordil	DMQESM7	Heart arrhythmia	BC65	Terminated	[8]

References

• [1] Treatment of congestive heart failure--current status of use of digitoxin. Eur J Clin Invest. 2001;31 Suppl 2:10-7.
• [2] Fab antibody fragments: some applications in clinical toxicology. Drug Saf. 2004;27(14):1115-33.
• [3] Medicinal plants in therapy. Bull World Health Organ. 1985;63(6):965-81.
• [4] First-in-human study of pbi-05204, an oleander-derived inhibitor of akt, fgf-2, nf- beta and p70s6k, in patients with advanced solid tumors. Invest New Drugs. 2014 Dec;32(6):1204-12.
• [5] Rostafuroxin: an ouabain antagonist that corrects renal and vascular Na+-K+- ATPase alterations in ouabain and adducin-dependent hypertension. Am J Physiol Regul Integr Comp Physiol. 2006 Mar;290(3):R529-35.
• [6] ClinicalTrials.gov (NCT03646071) A Study of RX108 in Patients With Locally Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health.
• [7] Novel analogues of istaroxime, a potent inhibitor of Na+,K+-ATPase: synthesis and structure-activity relationship. J Med Chem. 2008 Aug 14;51(15):4601-8.
• [8] WO patent application no. 1995,0085,58, Novel deoxy and oxygen-substituted sugar-containing 14-aminosteroid compounds.