Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR4VFOG)

• DOT Name: Appetite-regulating hormone (GHRL)
• Synonyms: Growth hormone secretagogue; Growth hormone-releasing peptide; Motilin-related peptide; Protein M46
• Gene Name: GHRL
• UniProt ID: GHRL_HUMAN
• PDB ID: 6H3E; 7F9Y; 7NA7; 7W2Z
• Pfam ID: PF04643 ; PF04644
• Sequence:
  MPSPGTVCSLLLLGMLWLDLAMAGSSFLSPEHQRVQQRKESKKPPAKLQPRALAGWLRPE
  DGGQAEGAEDELEVRFNAPFDVGIKLSGVQYQQHSQALGKFLQDILWEEAKEAPADK
• Function: [Ghrelin-27]: Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR). Induces the release of growth hormone from the pituitary. Has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion. Involved in growth regulation; [Ghrelin-28]: Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR). Induces the release of growth hormone from the pituitary. Has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion. Involved in growth regulation; [Obestatin]: May be the ligand for GPR39. May have an appetite-reducing effect resulting in decreased food intake. May reduce gastric emptying activity and jejunal motility.
• Tissue Specificity: Highest level in stomach. All forms are found in serum as well. Other tissues compensate for the loss of ghrelin synthesis in the stomach following gastrectomy.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Growth hormone synthesis, secretion and action (hsa04935)
• Reactome Pathway: Synthesis, secretion, and deacylation of Ghrelin (R-HSA-422085)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Appetite-regulating hormone (GHRL).	[1]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Appetite-regulating hormone (GHRL).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Appetite-regulating hormone (GHRL).	[2]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [3] Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.