Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD0IP9N)

• DOT Name: Gastrin (GAST)
• Gene Name: GAST
• UniProt ID: GAST_HUMAN
• PDB ID: 5WRJ; 7F8V; 7F8W; 7XOW
• Pfam ID: PF00918
• Sequence:
  MQRLCVYVLIFALALAAFSEASWKPRSQQPDAPLGTGANRDLELPWLEQQGPASHHRRQL
  GPQGPPHLVADPSKKQGPWLEEEEEAYGWMDFGRRSAEDEN
• Function: Gastrin stimulates the stomach mucosa to produce and secrete hydrochloric acid and the pancreas to secrete its digestive enzymes. It also stimulates smooth muscle contraction and increases blood circulation and water secretion in the stomach and intestine.
• KEGG Pathway: Gastric acid secretion (hsa04971)
• Reactome Pathway:
  Gastrin-CREB signalling pathway via PKC and MAPK (R-HSA-881907)
  G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Dexamethasone	DMMWZET	Approved	Gastrin (GAST) increases the Gastrointestinal disorders ADR of Dexamethasone.	[13]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Gastrin (GAST).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Gastrin (GAST).	[9]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Gastrin (GAST).	[2]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Gastrin (GAST).	[3]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Gastrin (GAST).	[4]
Cimetidine	DMH61ZB	Approved	Cimetidine affects the expression of Gastrin (GAST).	[5]
Lansoprazole	DMXYLQ3	Approved	Lansoprazole increases the expression of Gastrin (GAST).	[6]
Famotidine	DMRL3AB	Approved	Famotidine affects the expression of Gastrin (GAST).	[5]
Ranitidine	DM0GUSX	Approved	Ranitidine affects the expression of Gastrin (GAST).	[5]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Gastrin (GAST).	[8]
Calphostin C	DM9X2D0	Terminated	Calphostin C increases the expression of Gastrin (GAST).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Gastrin (GAST).	[11]
Lead acetate	DML0GZ2	Investigative	Lead acetate increases the expression of Gastrin (GAST).	[12]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Terbutaline	DMD4381	Approved	Terbutaline increases the secretion of Gastrin (GAST).	[7]
Forskolin	DM6ITNG	Investigative	Forskolin increases the secretion of Gastrin (GAST).	[7]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [4] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [5] Effects of three H2-receptor antagonists (cimetidine, famotidine, ranitidine) on serum gastrin level. Int J Clin Pharmacol Res. 2002;22(2):29-35.
• [6] Influence of lansoprazole on intragastric 24-hour pH, meal-stimulated gastric acid secretion, and concentrations of gastrointestinal hormones and enzymes in serum and gastric juice in healthy volunteers. Digestion. 1995;56(2):137-44. doi: 10.1159/000201233.
• [7] L-type calcium channels regulate gastrin release from human antral G cells. Am J Physiol. 1997 Aug;273(2 Pt 1):G281-8. doi: 10.1152/ajpgi.1997.273.2.G281.
• [8] Grape resveratrol increases serum adiponectin and downregulates inflammatory genes in peripheral blood mononuclear cells: a triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease. Cardiovasc Drugs Ther. 2013 Feb;27(1):37-48. doi: 10.1007/s10557-012-6427-8.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Targeting the beta-catenin/TCF transcriptional complex in the treatment of multiple myeloma. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7516-21. doi: 10.1073/pnas.0610299104. Epub 2007 Apr 23.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Pb2+ induces gastrin gene expression by extracellular signal-regulated kinases 1/2 and transcription factor activator protein 1 in human gastric carcinoma cells. Environ Toxicol. 2015 Feb;30(2):129-36. doi: 10.1002/tox.21878. Epub 2013 Jun 14.
• [13] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.