Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1GCG0L)

• DOT Name: Cholecystokinin (CCK)
• Synonyms: CCK
• Gene Name: CCK
• UniProt ID: CCKN_HUMAN
• PDB ID: 7EZH; 7EZK; 7EZM; 7MBX; 7MBY; 7XOU
• Pfam ID: PF00918
• Sequence:
  MNSGVCLCVLMAVLAAGALTQPVPPADPAGSGLQRAEEAPRRQLRVSQRTDGESRAHLGA
  LLARYIQQARKAPSGRMSIVKNLQNLDPSHRISDRDYMGWMDFGRRSAEEYEYPS
• Function: This peptide hormone induces gall bladder contraction and the release of pancreatic enzymes in the gut. Its function in the brain is not clear. Binding to CCK-A receptors stimulates amylase release from the pancreas, binding to CCK-B receptors stimulates gastric acid secretion.
• Tissue Specificity: Detected in cerebrospinal fluid and urine (at protein level).
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Insulin secretion (hsa04911)
  Pancreatic secretion (hsa04972)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

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 Cholecystokinin (CCK).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cholecystokinin (CCK).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cholecystokinin (CCK).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cholecystokinin (CCK).	[3]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Cholecystokinin (CCK).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cholecystokinin (CCK).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Cholecystokinin (CCK).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Cholecystokinin (CCK).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cholecystokinin (CCK).	[11]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Cholecystokinin (CCK).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Orlistat	DMRJSP8	Approved	Orlistat decreases the secretion of Cholecystokinin (CCK).	[8]
Octreotide	DMHIDCJ	Approved	Octreotide decreases the secretion of Cholecystokinin (CCK).	[9]

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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Research resource: STR DNA profile and gene expression comparisons of human BG-1 cells and a BG-1/MCF-7 clonal variant. Mol Endocrinol. 2014 Dec;28(12):2072-81.
• [5] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [6] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [7] The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet. 2009 Feb;41(2):178-186.
• [8] Orlistat inhibition of intestinal lipase acutely increases appetite and attenuates postprandial glucagon-like peptide-1-(7-36)-amide-1, cholecystokinin, and peptide YY concentrations. J Clin Endocrinol Metab. 2008 Oct;93(10):3995-8. doi: 10.1210/jc.2008-0924. Epub 2008 Jul 22.
• [9] Severe impairment of postprandial cholecystokinin release and gall-bladder emptying and high risk of gallstone formation in acromegalic patients during Sandostatin LAR. Aliment Pharmacol Ther. 2001 Feb;15(2):181-5. doi: 10.1046/j.1365-2036.2001.00924.x.
• [10] 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.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [12] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.