Target Information
| Target General Information | Top | |||||
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| Target ID |
T03917
(Former ID: TTDS00046)
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| Target Name |
Sodium/potassium-transporting ATPase (SPT ATPase)
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| Synonyms |
Na(+)/K(+) ATPase
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| Gene Name |
ATP1A1; ATP1A2; ATP1A3; ATP1B1; ATP1B2; ATP1B3
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Cardiac arrhythmia [ICD-11: BC9Z] | |||||
| 2 | Dental disease [ICD-11: DA08] | |||||
| 3 | Heart failure [ICD-11: BD10-BD1Z] | |||||
| 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.
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| BioChemical Class |
Acid anhydrides hydrolase
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| UniProt ID | ||||||
| Sequence |
MGKGVGRDKYEPAAVSEQGDKKGKKGKKDRDMDELKKEVSMDDHKLSLDELHRKYGTDLS
RGLTSARAAEILARDGPNALTPPPTTPEWIKFCRQLFGGFSMLLWIGAILCFLAYSIQAA TEEEPQNDNLYLGVVLSAVVIITGCFSYYQEAKSSKIMESFKNMVPQQALVIRNGEKMSI NAEEVVVGDLVEVKGGDRIPADLRIISANGCKVDNSSLTGESEPQTRSPDFTNENPLETR NIAFFSTNCVEGTARGIVVYTGDRTVMGRIATLASGLEGGQTPIAAEIEHFIHIITGVAV FLGVSFFILSLILEYTWLEAVIFLIGIIVANVPEGLLATVTVCLTLTAKRMARKNCLVKN LEAVETLGSTSTICSDKTGTLTQNRMTVAHMWFDNQIHEADTTENQSGVSFDKTSATWLA LSRIAGLCNRAVFQANQENLPILKRAVAGDASESALLKCIELCCGSVKEMRERYAKIVEI PFNSTNKYQLSIHKNPNTSEPQHLLVMKGAPERILDRCSSILLHGKEQPLDEELKDAFQN AYLELGGLGERVLGFCHLFLPDEQFPEGFQFDTDDVNFPIDNLCFVGLISMIDPPRAAVP DAVGKCRSAGIKVIMVTGDHPITAKAIAKGVGIISEGNETVEDIAARLNIPVSQVNPRDA KACVVHGSDLKDMTSEQLDDILKYHTEIVFARTSPQQKLIIVEGCQRQGAIVAVTGDGVN DSPALKKADIGVAMGIAGSDVSKQAADMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTL TSNIPEITPFLIFIIANIPLPLGTVTILCIDLGTDMVPAISLAYEQAESDIMKRQPRNPK TDKLVNERLISMAYGQIGMIQALGGFFTYFVILAENGFLPIHLLGLRVDWDDRWINDVED SYGQQWTYEQRKIVEFTCHTAFFVSIVVVQWADLVICKTRRNSVFQQGMKNKILIFGLFE ETALAAFLSYCPGMGVALRMYPLKPTWWFCAFPYSLLIFVYDEVRKLIIRRRPGGWVEKE TYY Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Digitoxin | Drug Info | Approved | Heart failure | [2], [3], [4] | |
| 2 | Digoxin | Drug Info | Approved | Heart failure | [5], [6] | |
| 3 | Sanguinarine | Drug Info | Approved | Dental plaque | [3] | |
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | PBI-05204 | Drug Info | Phase 2 | Solid tumour/cancer | [7] | |
| 2 | Rostafuroxin | Drug Info | Phase 2 | Hypertension | [8] | |
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | Istaroxime | Drug Info | Discontinued in Phase 2 | Cardiac disease | [10] | |
| 2 | Cordil | Drug Info | Terminated | Heart arrhythmia | [11] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 4 Inhibitor drugs | + | ||||
| 1 | Digitoxin | Drug Info | [1] | |||
| 2 | Digoxin | Drug Info | [12] | |||
| 3 | PBI-05204 | Drug Info | [14] | |||
| 4 | Istaroxime | Drug Info | [16] | |||
| Modulator | [+] 3 Modulator drugs | + | ||||
| 1 | Sanguinarine | Drug Info | [13] | |||
| 2 | Rostafuroxin | Drug Info | [15] | |||
| 3 | Cordil | Drug Info | [17] | |||
| 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 | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 17 KEGG Pathways | + | ||||
| 1 | cGMP-PKG signaling pathway | |||||
| 2 | cAMP signaling pathway | |||||
| 3 | Cardiac muscle contraction | |||||
| 4 | Adrenergic signaling in cardiomyocytes | |||||
| 5 | Insulin secretion | |||||
| 6 | Thyroid hormone synthesis | |||||
| 7 | Thyroid hormone signaling pathway | |||||
| 8 | Aldosterone-regulated sodium reabsorption | |||||
| 9 | Endocrine and other factor-regulated calcium reabsorption | |||||
| 10 | Proximal tubule bicarbonate reclamation | |||||
| 11 | Salivary secretion | |||||
| 12 | Gastric acid secretion | |||||
| 13 | Pancreatic secretion | |||||
| 14 | Carbohydrate digestion and absorption | |||||
| 15 | Protein digestion and absorption | |||||
| 16 | Bile secretion | |||||
| 17 | Mineral absorption | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Treatment of congestive heart failure--current status of use of digitoxin. Eur J Clin Invest. 2001;31 Suppl 2:10-7. | |||||
| 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: 6782). | |||||
| REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 4 | Cardiac glycosides provide neuroprotection against ischemic stroke: discovery by a brain slice-based compound screening platform. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10461-10466. | |||||
| REF 5 | 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: 4726). | |||||
| REF 6 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 021648. | |||||
| REF 7 | ClinicalTrials.gov (NCT02329717) Efficacy and Safety Study of PBI-05204 in Patients With Stage IV Metastatic Pancreatic Adenocarcinoma. U.S. National Institutes of Health. | |||||
| REF 8 | ClinicalTrials.gov (NCT01320397) Antihypertensive Effect of Rostafuroxin Compared With Losartan in Hypertensive Patients Bearing Specified Gene Mutations. U.S. National Institutes of Health. | |||||
| REF 9 | ClinicalTrials.gov (NCT03646071) A Study of RX108 in Patients With Locally Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010607) | |||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001241) | |||||
| REF 12 | Fab antibody fragments: some applications in clinical toxicology. Drug Saf. 2004;27(14):1115-33. | |||||
| REF 13 | Medicinal plants in therapy. Bull World Health Organ. 1985;63(6):965-81. | |||||
| REF 14 | 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. | |||||
| REF 15 | 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. | |||||
| REF 16 | 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. | |||||
| REF 17 | WO patent application no. 1995,0085,58, Novel deoxy and oxygen-substituted sugar-containing 14-aminosteroid compounds. | |||||
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