Target Information
| Target General Information | Top | |||||
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| Target ID |
T92687
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| Target Name |
Gastric H(+)/K(+) ATPase (Proton pump)
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| Synonyms |
Proton pump; Potassium-transporting ATPase
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| Gene Name |
ATP4A; ATP4B
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 4 Target-related Diseases | + | ||||
| 1 | Gastro-oesophageal reflux disease [ICD-11: DA22] | |||||
| 2 | Helicobacter infection [ICD-11: DA42-DA63] | |||||
| 3 | Oesophageal ulcer [ICD-11: DA25] | |||||
| 4 | Peptic ulcer [ICD-11: DA61] | |||||
| Function |
Proton pump of the stomach. Exchanges potassium from the intestinal lumen with cytoplasmic hydronium and is the enzyme primarily responsible for the acidification of the stomach contents and the activation of the digestive enzyme pepsin.
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| UniProt ID | ||||||
| Sequence |
MGKAENYELYSVELGPGPGGDMAAKMSKKKKAGGGGGKRKEKLENMKKEMEINDHQLSVA
ELEQKYQTSATKGLSASLAAELLLRDGPNALRPPRGTPEYVKFARQLAGGLQCLMWVAAA ICLIAFAIQASEGDLTTDDNLYLAIALIAVVVVTGCFGYYQEFKSTNIIASFKNLVPQQA TVIRDGDKFQINADQLVVGDLVEMKGGDRVPADIRILAAQGCKVDNSSLTGESEPQTRSP ECTHESPLETRNIAFFSTMCLEGTVQGLVVNTGDRTIIGRIASLASGVENEKTPIAIEIE HFVDIIAGLAILFGATFFIVAMCIGYTFLRAMVFFMAIVVAYVPEGLLATVTVCLSLTAK RLASKNCVVKNLEAVETLGSTSVICSDKTGTLTQNRMTVSHLWFDNHIHTADTTEDQSGQ TFDQSSETWRALCRVLTLCNRAAFKSGQDAVPVPKRIVIGDASETALLKFSELTLGNAMG YRDRFPKVCEIPFNSTNKFQLSIHTLEDPRDPRHLLVMKGAPERVLERCSSILIKGQELP LDEQWREAFQTAYLSLGGLGERVLGFCQLYLNEKDYPPGYAFDVEAMNFPSSGLCFAGLV SMIDPPRATVPDAVLKCRTAGIRVIMVTGDHPITAKAIAASVGIISEGSETVEDIAARLR VPVDQVNRKDARACVINGMQLKDMDPSELVEALRTHPEMVFARTSPQQKLVIVESCQRLG AIVAVTGDGVNDSPALKKADIGVAMGIAGSDAAKNAADMILLDDNFASIVTGVEQGRLIF DNLKKSIAYTLTKNIPELTPYLIYITVSVPLPLGCITILFIELCTDIFPSVSLAYEKAES DIMHLRPRNPKRDRLVNEPLAAYSYFQIGAIQSFAGFTDYFTAMAQEGWFPLLCVGLRAQ WEDHHLQDLQDSYGQEWTFGQRLYQQYTCYTVFFISIEVCQIADVLIRKTRRLSAFQQGF FRNKILVIAIVFQVCIGCFLCYCPGMPNIFNFMPIRFQWWLVPLPYGILIFVYDEIRKLG VRCCPGSWWDQELYY Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 5 Approved Drugs | + | ||||
| 1 | Dexlansoprazole | Drug Info | Approved | Non-erosive gastro-esophageal reflux disease | [2] | |
| 2 | Esomeprazole | Drug Info | Approved | Peptic ulcer | [3], [4] | |
| 3 | Omeprazole | Drug Info | Approved | Gastroesophageal reflux disease | [5], [6] | |
| 4 | Pantoprazole | Drug Info | Approved | Gastroesophageal reflux disease | [7], [8] | |
| 5 | Vonoprazan | Drug Info | Approved | Helicobacter infection | [9] | |
| Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
| 1 | RQ-00000004 | Drug Info | Phase 3 | Gastroesophageal reflux disease | [10] | |
| 2 | AZD-0865 | Drug Info | Phase 2 | Gastrointestinal disease | [11] | |
| 3 | S-tenatoprazole | Drug Info | Phase 2 | Peptic ulcer | [12] | |
| 4 | YH-4808 | Drug Info | Phase 2 | Duodenal ulcer | [13] | |
| Discontinued Drug(s) | [+] 10 Discontinued Drugs | + | ||||
| 1 | LEMINOPRAZOLE | Drug Info | Discontinued in Preregistration | Ulcerative colitis | [14] | |
| 2 | PUMAPRAZOLE | Drug Info | Discontinued in Phase 3 | Duodenal ulcer | [15] | |
| 3 | SKF-96067 | Drug Info | Discontinued in Phase 3 | Peptic ulcer | [16] | |
| 4 | AR-H047108 | Drug Info | Discontinued in Phase 2 | Duodenal ulcer | [17] | |
| 5 | SORAPRAZAN | Drug Info | Discontinued in Phase 2 | Peptic ulcer | [18] | |
| 6 | TY-11345 | Drug Info | Discontinued in Phase 2 | Peptic ulcer | [19] | |
| 7 | CS-526 | Drug Info | Discontinued in Phase 1 | Gastroesophageal reflux disease | [20] | |
| 8 | SKF-97574 | Drug Info | Discontinued in Phase 1 | Peptic ulcer | [21] | |
| 9 | Saviprazole | Drug Info | Terminated | Peptic ulcer | [22] | |
| 10 | SK&F-95601 | Drug Info | Terminated | Peptic ulcer | [23] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 20 Modulator drugs | + | ||||
| 1 | Dexlansoprazole | Drug Info | [1] | |||
| 2 | Esomeprazole | Drug Info | [1] | |||
| 3 | Omeprazole | Drug Info | [1] | |||
| 4 | Pantoprazole | Drug Info | [1] | |||
| 5 | Vonoprazan | Drug Info | [9] | |||
| 6 | RQ-00000004 | Drug Info | [24] | |||
| 7 | AZD-0865 | Drug Info | [25] | |||
| 8 | S-tenatoprazole | Drug Info | [26] | |||
| 9 | YH-4808 | Drug Info | [27] | |||
| 10 | LEMINOPRAZOLE | Drug Info | [28] | |||
| 11 | PUMAPRAZOLE | Drug Info | [29] | |||
| 12 | SKF-96067 | Drug Info | [30] | |||
| 13 | AR-H047108 | Drug Info | [31] | |||
| 14 | SORAPRAZAN | Drug Info | [32] | |||
| 15 | TY-11345 | Drug Info | [33] | |||
| 16 | CS-526 | Drug Info | [34] | |||
| 17 | SKF-97574 | Drug Info | [30] | |||
| 18 | Saviprazole | Drug Info | [35] | |||
| 19 | SK&F-95601 | Drug Info | [36] | |||
| 20 | YH-1238 | Drug Info | [37] | |||
| 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 | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 2 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 022287. | |||||
| REF 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. (Ligand id: 5488). | |||||
| REF 4 | Esomeprazole: a review of its use in the management of gastric acid-related diseases in adults. Drugs. 2008;68(11):1571-607. | |||||
| 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: 4279). | |||||
| REF 6 | Generic omeprazole delayed-release capsules: in vitro performance evaluations. Drug Dev Ind Pharm. 2009 Aug;35(8):917-21. | |||||
| 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. (Ligand id: 7260). | |||||
| REF 8 | An overview of proton pump inhibitors. Gastroenterol Nurs. 2003 Sep-Oct;26(5):182-90. | |||||
| REF 9 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2008 | |||||
| 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 800033657) | |||||
| REF 11 | ClinicalTrials.gov (NCT00206284) A Dose-finding Phase IIb Study With AZD0865 and Esomeprazole in GERD Patients Without Erosive Esophagitis.. U.S. National Institutes of Health. | |||||
| REF 12 | ClinicalTrials.gov (NCT00282555) Efficiency Study of S-Tenatoprazole-Na to Treat Erosive or Ulcerative Esophagitis. U.S. National Institutes of Health. | |||||
| REF 13 | ClinicalTrials.gov (NCT01538849) Study to Investigate the Safety, Tolerability and Efficacy of YH4808 in Patients With Reflux Esophagitis. U.S. National Institutes of Health. | |||||
| REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000604) | |||||
| REF 15 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005537) | |||||
| REF 16 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001218) | |||||
| REF 17 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013302) | |||||
| REF 18 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015211) | |||||
| REF 19 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001313) | |||||
| REF 20 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015294) | |||||
| REF 21 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001921) | |||||
| REF 22 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000579) | |||||
| REF 23 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000578) | |||||
| REF 24 | N-(2-hydroxyethyl)-N,2-dimethyl-8-{[(4R)-5-methyl-3,4-dihydro-2H-chromen-4-yl]amino}imidazo[1,2-a]pyridine-6-carboxamide (PF-03716556), a novel, potent, and selective acid pump antagonist for the treatment of gastroesophageal reflux disease. J Pharmacol Exp Ther. 2009 Feb;328(2):671-9. | |||||
| REF 25 | Mechanism of action of AZD0865, a K+-competitive inhibitor of gastric H+,K+-ATPase. Biochem Pharmacol. 2007 Jan 15;73(2):198-205. | |||||
| REF 26 | Tenatoprazole, a novel proton pump inhibitor with a prolonged plasma half-life: effects on intragastric pH and comparison with esomeprazole in heal... Aliment Pharmacol Ther. 2004 Mar 15;19(6):655-62. | |||||
| REF 27 | Poor effectiveness of proton pump inhibitors in non-erosive reflux disease: the truth in the end! Neurogastroenterol Motil.2012 Aug;24(8):697-704. | |||||
| REF 28 | Vasoinhibitory effect of leminoprazole, a H+,K(+)-ATPase inhibitor, on rat aortic rings. Gen Pharmacol. 1996 Jan;27(1):117-21. | |||||
| REF 29 | Effects of pumaprazole (BY841), a novel reversible proton pump antagonist, and of omeprazole, on intragastric acidity before and after cure of Heli... Aliment Pharmacol Ther. 1999 Jan;13(1):27-34. | |||||
| REF 30 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 31 | Early stellate cell activation and veno-occlusive-disease (VOD)-like hepatotoxicity in dogs treated with AR-H047108, an imidazopyridine proton pump inhibitor.Toxicol Pathol.2008 Jul;36(5):727-37. | |||||
| REF 32 | Soraprazan: setting new standards in inhibition of gastric acid secretion.J Pharmacol Exp Ther.2007 Jun;321(3):866-74. | |||||
| REF 33 | Biochemical and pharmacological properties of a newly synthesized proton pump (H+/K(+)-ATPase) inhibitor, TY-11345 in experimental animals. Jpn J Pharmacol. 1993 Aug;62(4):363-71. | |||||
| REF 34 | Pharmacological profile of novel acid pump antagonist 7-(4-fluorobenzyloxy)-2,3-dimethyl-1-{[(1S,2S)-2-methyl cyclopropyl]methyl}-1H-pyrrolo[2,3-d]... J Pharmacol Exp Ther. 2007 Oct;323(1):308-17. | |||||
| REF 35 | Gastric acid inhibitory profile of saviprazole (HOE 731) compared to omeprazole. Pharmacology. 1991;43(6):293-303. | |||||
| REF 36 | 2-[[(4-Amino-2-pyridyl)methyl]sulfinyl]benzimidazole H+/K+-ATPase inhibitors.The relationship between pyridine basicity, stability, and activity.J Med Chem.1989 Aug;32(8):1970-7. | |||||
| REF 37 | Compositions for improving gastrointestinal nutrient and drug absorption | |||||
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