Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTF1QVM)

• DTT Name: Gastric H(+)/K(+) ATPase alpha (ATP4A)
• Synonyms: Gastric H+/K+ ATPase alpha subunit; Gastric H(+)/K(+)-ATPase; ATP4A
• Gene Name: ATP4A
• DTT Type: Successful target; [1]
• BioChemical Class: Acid anhydrides hydrolase
• UniProt ID: ATP4A_HUMAN
• TTD ID: T51666
• EC Number: EC 7.2.2.19
• Sequence:
  MGKAENYELYSVELGPGPGGDMAAKMSKKKKAGGGGGKRKEKLENMKKEMEINDHQLSVA
  ELEQKYQTSATKGLSASLAAELLLRDGPNALRPPRGTPEYVKFARQLAGGLQCLMWVAAA
  ICLIAFAIQASEGDLTTDDNLYLAIALIAVVVVTGCFGYYQEFKSTNIIASFKNLVPQQA
  TVIRDGDKFQINADQLVVGDLVEMKGGDRVPADIRILAAQGCKVDNSSLTGESEPQTRSP
  ECTHESPLETRNIAFFSTMCLEGTVQGLVVNTGDRTIIGRIASLASGVENEKTPIAIEIE
  HFVDIIAGLAILFGATFFIVAMCIGYTFLRAMVFFMAIVVAYVPEGLLATVTVCLSLTAK
  RLASKNCVVKNLEAVETLGSTSVICSDKTGTLTQNRMTVSHLWFDNHIHTADTTEDQSGQ
  TFDQSSETWRALCRVLTLCNRAAFKSGQDAVPVPKRIVIGDASETALLKFSELTLGNAMG
  YRDRFPKVCEIPFNSTNKFQLSIHTLEDPRDPRHLLVMKGAPERVLERCSSILIKGQELP
  LDEQWREAFQTAYLSLGGLGERVLGFCQLYLNEKDYPPGYAFDVEAMNFPSSGLCFAGLV
  SMIDPPRATVPDAVLKCRTAGIRVIMVTGDHPITAKAIAASVGIISEGSETVEDIAARLR
  VPVDQVNRKDARACVINGMQLKDMDPSELVEALRTHPEMVFARTSPQQKLVIVESCQRLG
  AIVAVTGDGVNDSPALKKADIGVAMGIAGSDAAKNAADMILLDDNFASIVTGVEQGRLIF
  DNLKKSIAYTLTKNIPELTPYLIYITVSVPLPLGCITILFIELCTDIFPSVSLAYEKAES
  DIMHLRPRNPKRDRLVNEPLAAYSYFQIGAIQSFAGFTDYFTAMAQEGWFPLLCVGLRAQ
  WEDHHLQDLQDSYGQEWTFGQRLYQQYTCYTVFFISIEVCQIADVLIRKTRRLSAFQQGF
  FRNKILVIAIVFQVCIGCFLCYCPGMPNIFNFMPIRFQWWLVPLPYGILIFVYDEIRKLG
  VRCCPGSWWDQELYY
• Function: Catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. Responsible for acid production in the stomach.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Collecting duct acid secretion (hsa04966)
  Gastric acid secretion (hsa04971)
• Reactome Pathway: Ion transport by P-type ATPases (R-HSA-936837)
• BioCyc Pathway: MetaCyc:HS02790-MON

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dexlansoprazole	DM1DBV5	Erosive esophagitis	DA25.0	Approved	[2]
Rabeprazole	DMMZXIW	Bacterial infection	1A00-1C4Z	Approved	[1]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AG-SPT201	DMJRQDG	Ulcerative colitis	DD71	Phase 3	[3]
API-023	DM6P93J	Gastroesophageal reflux disease	DA22.Z	Phase 1	[4]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Saliphenylhalamide	DMLMRGH	Solid tumour/cancer	2A00-2F9Z	Preclinical	[4]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARH-1029	DM8NETP	Helicobacter infection	DA42-DA63	Investigative	[4]
CA-50040	DMCLN6M	Colorectal cancer	2B91.Z	Investigative	[4]
CDRI-85/92	DMQDA5W	Stomach ulcer	DA60.Z	Investigative	[4]
OPC-22575	DMO4WH9	Ulcerative colitis	DD71	Investigative	[4]
PA-10040	DMELTM2	Cardiovascular disease	BA00-BE2Z	Investigative	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rectal cancer	2C82	Rectal colon tissue	1.42E-02	-0.15	-1.5

References

• [1] Review article: rabeprazole's tolerability profile in clinical trials. Aliment Pharmacol Ther. 1999 Oct;13 Suppl 5:17-23.
• [2] Clinical pipeline report, company report or official report of Takeda (2009).
• [3] Effects of pantoprazole, a novel H+/K+-ATPase inhibitor, on duodenal ulcerogenic and healing responses in rats: a comparative study with omeprazole and lansoprazole. J Gastroenterol Hepatol. 1999 Mar;14(3):251-7.
• [4] 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: 849).