Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUFSTG9)

• DOT Name: Gastric inhibitory polypeptide (GIP)
• Synonyms: GIP; Glucose-dependent insulinotropic polypeptide; Incretin hormone
• Gene Name: GIP
• UniProt ID: GIP_HUMAN
• PDB ID: 1T5Q; 2B4N; 2L70; 2L71; 2OBU; 2QKH; 7DTY; 7RA3
• Pfam ID: PF00123
• Sequence:
  MVATKTFALLLLSLFLAVGLGEKKEGHFSALPSLPVGSHAKVSSPQPRGPRYAEGTFISD
  YSIAMDKIHQQDFVNWLLAQKGKKNDWKHNITQREARALELASQANRKEEEAVEPQSSPA
  KNPSDEDLLRDLLIQELLACLLDQTNLCRLRSR
• Function: Potent stimulator of insulin secretion and relatively poor inhibitor of gastric acid secretion.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Insulin secretion (hsa04911)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Glucagon-type ligand receptors (R-HSA-420092)
  Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) (R-HSA-400511)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Gastric inhibitory polypeptide (GIP).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Gastric inhibitory polypeptide (GIP).	[2]
Orlistat	DMRJSP8	Approved	Orlistat decreases the expression of Gastric inhibitory polypeptide (GIP).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Gastric inhibitory polypeptide (GIP).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Metoclopramide	DMFA5MY	Approved	Metoclopramide increases the secretion of Gastric inhibitory polypeptide (GIP).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Gastric inhibitory polypeptide (GIP).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Gastric inhibitory polypeptide (GIP).	[7]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Effect of lipase inhibition on gastric emptying of, and the glycemic and incretin responses to, an oil/aqueous drink in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2003 Aug;88(8):3829-34. doi: 10.1210/jc.2003-030199.
• [4] Effects of metoclopramide on duodenal motility and flow events, glucose absorption, and incretin hormone release in response to intraduodenal glucose infusion. Am J Physiol Gastrointest Liver Physiol. 2010 Dec;299(6):G1326-33. doi: 10.1152/ajpgi.00476.2009. Epub 2010 Sep 9.
• [5] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [6] 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.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.