Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBQVXY5)

• DOT Name: Sushi, nidogen and EGF-like domain-containing protein 1 (SNED1)
• Synonyms: Insulin-responsive sequence DNA-binding protein 1; IRE-BP1
• Gene Name: SNED1
• Related Disease:
  IgA nephropathy
  Adenocarcinoma
  Adenoma
  Adult glioblastoma
  Bipolar disorder
  Carcinoma
  Colon cancer
  Colon carcinoma
  Familial adenomatous polyposis
  Glioblastoma multiforme
  Major depressive disorder
  Medulloblastoma
  Metastatic malignant neoplasm
  Neoplasm
  Obesity
  Pituitary adenoma
  Schizophrenia
  Squamous cell carcinoma
  Type-1/2 diabetes
  Neuroendocrine neoplasm
  Hyperglycemia
  Prostate carcinoma
  Seminoma
• UniProt ID: SNED1_HUMAN
• Pfam ID: PF00008 ; PF00041 ; PF12661 ; PF06119
• Sequence:
  MRHGVAWALLVAAALGLGARGVRGAVALADFYPFGAERGDAVTPKQDDGGSGLRPLSVPF
  PFFGAEHSGLYVNNNGIISFLKEVSQFTPVAFPIAKDRCVVAAFWADVDNRRAGDVYYRE
  ATDPAMLRRATEDVRHYFPELLDFNATWVFVATWYRVTFFGGSSSSPVNTFQTVLITDGK
  LSFTIFNYESIVWTTGTHASSGGNATGLGGIAAQAGFNAGDGQRYFSIPGSRTADMAEVE
  TTTNVGVPGRWAFRIDDAQVRVGGCGHTTSVCLALRPCLNGGKCIDDCVTGNPSYTCSCL
  SGFTGRRCHLDVNECASQPCQNGGTCTHGINSFRCQCPAGFGGPTCETAQSPCDTKECQH
  GGQCQVENGSAVCVCQAGYTGAACEMDVDDCSPDPCLNGGSCVDLVGNYTCLCAEPFKGL
  RCETGDHPVPDACLSAPCHNGGTCVDADQGYVCECPEGFMGLDCRERVPDDCECRNGGRC
  LGANTTLCQCPLGFFGLLCEFEITAMPCNMNTQCPDGGYCMEHGGSYLCVCHTDHNASHS
  LPSPCDSDPCFNGGSCDAHDDSYTCECPRGFHGKHCEKARPHLCSSGPCRNGGTCKEAGG
  EYHCSCPYRFTGRHCEIGKPDSCASGPCHNGGTCFHYIGKYKCDCPPGFSGRHCEIAPSP
  CFRSPCVNGGTCEDRDTDFFCHCQAGYMGRRCQAEVDCGPPEEVKHATLRFNGTRLGAVA
  LYACDRGYSLSAPSRIRVCQPHGVWSEPPQCLEIDECRSQPCLHGGSCQDRVAGYLCLCS
  TGYEGAHCELERDECRAHPCRNGGSCRNLPGAYVCRCPAGFVGVHCETEVDACDSSPCQH
  GGRCESGGGAYLCVCPESFFGYHCETVSDPCFSSPCGGRGYCLASNGSHSCTCKVGYTGE
  DCAKELFPPTALKMERVEESGVSISWNPPNGPAARQMLDGYAVTYVSSDGSYRRTDFVDR
  TRSSHQLQALAAGRAYNISVFSVKRNSNNKNDISRPAVLLARTRPRPVEGFEVTNVTAST
  ISVQWALHRIRHATVSGVRVSIRHPEALRDQATDVDRSVDRFTFRALLPGKRYTIQLTTL
  SGLRGEEHPTESLATAPTHVWTRPLPPANLTAARVTATSAHVVWDAPTPGSLLEAYVINV
  TTSQSTKSRYVPNGKLASYTVRDLLPGRRYQLSVIAVQSTELGPQHSEPAHLYIITSPRD
  GADRRWHQGGHHPRVLKNRPPPARLPELRLLNDHSAPETPTQPPRFSELVDGRGRVSARF
  GGSPSKAATVRSQPTASAQLENMEEAPKRVSLALQLPEHGSKDIGNVPGNCSENPCQNGG
  TCVPGADAHSCDCGPGFKGRRCELACIKVSRPCTRLFSETKAFPVWEGGVCHHVYKRVYR
  VHQDICFKESCESTSLKKTPNRKQSKSQTLEKS

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
IgA nephropathy	DISZ8MTK	Definitive	Altered Expression	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Adenoma	DIS78ZEV	Strong	Altered Expression	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[3]
Colon cancer	DISVC52G	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[6]
Familial adenomatous polyposis	DISW53RE	Strong	Altered Expression	[3]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[5]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[4]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Obesity	DIS47Y1K	Strong	Biomarker	[8]
Pituitary adenoma	DISJ5R1X	Strong	Biomarker	[9]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[5]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[2]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[8]
Neuroendocrine neoplasm	DISNPLOO	moderate	Biomarker	[10]
Hyperglycemia	DIS0BZB5	Limited	Altered Expression	[11]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[12]
Seminoma	DIS3J8LJ	Limited	Biomarker	[13]

3 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 Sushi, nidogen and EGF-like domain-containing protein 1 (SNED1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sushi, nidogen and EGF-like domain-containing protein 1 (SNED1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Sushi, nidogen and EGF-like domain-containing protein 1 (SNED1).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Sushi, nidogen and EGF-like domain-containing protein 1 (SNED1).	[15]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Sushi, nidogen and EGF-like domain-containing protein 1 (SNED1).	[16]

References

• [1] Expression of somatostatin and somatostatin receptor subtypes 1-5 in human normal and diseased kidney.J Histochem Cytochem. 2008 Aug;56(8):733-43. doi: 10.1369/jhc.2008.950998. Epub 2008 Apr 28.
• [2] Somatostatin and CXCR4 expression patterns in adenocarcinoma and squamous cell carcinoma of the lung relative to small cell lung cancer.J Cancer Res Clin Oncol. 2018 Oct;144(10):1921-1932. doi: 10.1007/s00432-018-2722-5. Epub 2018 Aug 3.
• [3] Loss of sst2 somatostatin receptor gene expression in human pancreatic and colorectal cancer.Cancer Res. 1996 Apr 15;56(8):1823-7.
• [4] Comparison of somatostatin receptor expression in human gliomas and medulloblastomas.J Neuroendocrinol. 2002 Jun;14(6):458-71. doi: 10.1046/j.1365-2826.2002.00801.x.
• [5] Genome-wide association study identifies common variants associated with pharmacokinetics of psychotropic drugs.J Psychopharmacol. 2015 Aug;29(8):884-91. doi: 10.1177/0269881115584469. Epub 2015 May 5.
• [6] Somatostatin inhibits colon cancer cell growth through cyclooxygenase-2 downregulation.Br J Pharmacol. 2008 Sep;155(2):198-209. doi: 10.1038/bjp.2008.268. Epub 2008 Jun 30.
• [7] Clinical and functional implication of the components of somatostatin system in gastroenteropancreatic neuroendocrine tumors.Endocrine. 2018 Feb;59(2):426-437. doi: 10.1007/s12020-017-1482-3. Epub 2017 Dec 1.
• [8] Regulation of insulin-response element binding protein-1 in obesity and diabetes: potential role in impaired insulin-induced gene transcription.Endocrinology. 2008 Oct;149(10):4829-36. doi: 10.1210/en.2007-1693. Epub 2008 Jun 19.
• [9] A Critical Evaluation of sst3 and sst5 Immunohistochemistry in Human Pituitary Adenomas.Neuroendocrinology. 2018;106(2):116-127. doi: 10.1159/000472563. Epub 2017 Apr 7.
• [10] Somatostatin receptors.Digestion. 2000;62 Suppl 1:27-32. doi: 10.1159/000051852.
• [11] Over-expression of insulin-response element binding protein-1 (IRE-BP1) in mouse pancreatic islets increases expression of RACK1 and TCTP: Beta cell markers of high glucose sensitivity.Biochim Biophys Acta Proteins Proteom. 2017 Feb;1865(2):186-194. doi: 10.1016/j.bbapap.2016.10.015. Epub 2016 Nov 3.
• [12] Radiogenomics Consortium Genome-Wide Association Study Meta-Analysis of Late Toxicity After Prostate Cancer Radiotherapy.J Natl Cancer Inst. 2020 Feb 1;112(2):179-190. doi: 10.1093/jnci/djz075.
• [13] Somatostatin receptor expression profile as a potential criterion for discrimination between seminoma and non-seminoma testicular tumors.Cancer Detect Prev. 2001;25(5):446-53.
• [14] 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.
• [15] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [16] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [17] 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.
• [18] 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.