Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY75GQH)

• DOT Name: Somatostatin (SST)
• Synonyms: Growth hormone release-inhibiting factor
• Gene Name: SST
• UniProt ID: SMS_HUMAN
• PDB ID: 2MI1; 7T10; 7WIC; 7WJ5; 7XAT; 7XMR; 7XMS; 7Y27
• Pfam ID: PF03002
• Sequence:
  MLSCRLQCALAALSIVLALGCVTGAPSDPRLRQFLQKSLAAAAGKQELAKYFLAELLSEP
  NQTENDALEPEDLSQAAEQDEMRLELQRSANSNPAMAPRERKAGCKNFFWKTFTSC
• Function: [Somatostatin-14]: Inhibits the secretion of pituitary hormones, including that of growth hormone/somatotropin (GH1), PRL, ACTH, luteinizing hormone (LH) and TSH. Also impairs ghrelin- and GnRH-stimulated secretion of GH1 and LH; the inhibition of ghrelin-stimulated secretion of GH1 can be further increased by neuronostatin; [Neuronostatin]: May enhance low-glucose-induced glucagon release by pancreatic alpha cells. This effect may be mediated by binding to GPR107 and PKA activation. May regulate cardiac contractile function. May compromise cardiomyocyte viability. In the central nervous system, may impair memory retention and may affect hippocampal excitability. May also have anxiolytic and anorexigenic effects. May play a role in arterial pressure regulation. May inhibit basal, but not ghrelin- or GnRH-stimulated secretion of GH1 or LH, but does not affect the release of other pituitary hormones, including PRL, ACTH, FSH or TSH. Potentiates inhibitory action of somatostatin on ghrelin-stimulated secretion of GH1, but not that on GnRH-stimulated secretion of LH.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Growth hormone synthesis, secretion and action (hsa04935)
  Gastric acid secretion (hsa04971)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  MECP2 regulates transcription of neuronal ligands (R-HSA-9022702)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Somatostatin (SST).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Somatostatin (SST).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Somatostatin (SST).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Somatostatin (SST).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Somatostatin (SST).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Somatostatin (SST).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Somatostatin (SST).	[7]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Somatostatin (SST).	[9]
Menadione	DMSJDTY	Approved	Menadione decreases the expression of Somatostatin (SST).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Somatostatin (SST).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Somatostatin (SST).	[11]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Somatostatin (SST).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Somatostatin (SST).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Somatostatin (SST).	[15]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Somatostatin (SST).	[16]
tryptanthrin	DMTRYCI	Investigative	tryptanthrin increases the expression of Somatostatin (SST).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Somatostatin (SST).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Somatostatin (SST).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Octreotide	DMHIDCJ	Approved	Octreotide decreases the secretion of Somatostatin (SST).	[13]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the secretion of Somatostatin (SST).	[13]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] Hypermethylation of the somatostatin promoter is a common, early event in human esophageal carcinogenesis. Cancer. 2008 Jan 1;112(1):43-9. doi: 10.1002/cncr.23135.
• [9] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [12] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [13] Characterization of the functional and growth properties of long-term cell cultures established from a human somatostatinoma. Endocr Relat Cancer. 2006 Mar;13(1):79-93. doi: 10.1677/erc.1.00988.
• [14] 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.
• [15] 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.
• [16] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [17] Tryptanthrin induces growth inhibition and neuronal differentiation in the human neuroblastoma LA-N-1 cells. Chem Biol Interact. 2013 Apr 25;203(2):512-21. doi: 10.1016/j.cbi.2013.03.001. Epub 2013 Mar 13.