Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFAGWO7)

• DOT Name: Somatostatin receptor type 1 (SSTR1)
• Synonyms: SS-1-R; SS1-R; SS1R; SST1; SRIF-2
• Gene Name: SSTR1
• UniProt ID: SSR1_HUMAN
• Pfam ID: PF00001
• Sequence:
  MFPNGTASSPSSSPSPSPGSCGEGGGSRGPGAGAADGMEEPGRNASQNGTLSEGQGSAIL
  ISFIYSVVCLVGLCGNSMVIYVILRYAKMKTATNIYILNLAIADELLMLSVPFLVTSTLL
  RHWPFGALLCRLVLSVDAVNMFTSIYCLTVLSVDRYVAVVHPIKAARYRRPTVAKVVNLG
  VWVLSLLVILPIVVFSRTAANSDGTVACNMLMPEPAQRWLVGFVLYTFLMGFLLPVGAIC
  LCYVLIIAKMRMVALKAGWQQRKRSERKITLMVMMVVMVFVICWMPFYVVQLVNVFAEQD
  DATVSQLSVILGYANSCANPILYGFLSDNFKRSFQRILCLSWMDNAAEEPVDYYATALKS
  RAYSVEDFQPENLESGGVFRNGTCTSRITTL
• Function: Receptor for somatostatin with higher affinity for somatostatin-14 than -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and Na(+)/H(+) exchanger via pertussis toxin insensitive G proteins.
• Tissue Specificity: Fetal kidney, fetal liver, and adult pancreas, brain, lung, jejunum and stomach.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Growth hormone synthesis, secretion and action (hsa04935)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

7 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 Somatostatin receptor type 1 (SSTR1).	[1]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Somatostatin receptor type 1 (SSTR1).	[2]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Somatostatin receptor type 1 (SSTR1).	[3]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Somatostatin receptor type 1 (SSTR1).	[4]
AZD-4877	DMFVL5J	Phase 2	AZD-4877 decreases the activity of Somatostatin receptor type 1 (SSTR1).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Somatostatin receptor type 1 (SSTR1).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Somatostatin receptor type 1 (SSTR1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Pasireotide	DMHM7JS	Approved	Pasireotide affects the binding of Somatostatin receptor type 1 (SSTR1).	[5]

1 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 Somatostatin receptor type 1 (SSTR1).	[7]

References

• [1] 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.
• [2] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [3] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [4] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [5] Medicinal chemistry of somatostatin analogs leading to the DTPA and DOTA conjugates of the multi-receptor-ligand SOM230. J Endocrinol Invest. 2005;28(11 Suppl International):15-20.
• [6] Discovery of (+)-N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877), a kinesin spindle protein inhibitor and potential anticancer agent. J Med Chem. 2011 Oct 13;54(19):6734-50. doi: 10.1021/jm200629m. Epub 2011 Sep 7.
• [7] 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.
• [8] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [9] 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.