Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBHAW5K)

• DOT Name: Somatomedin-B and thrombospondin type-1 domain-containing protein (SBSPON)
• Synonyms: RPE-spondin
• Gene Name: SBSPON
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Crohn disease
• UniProt ID: SBSPO_HUMAN
• Pfam ID: PF19028
• Sequence:
  MRTLWMALCALSRLWPGAQAGCAEAGRCCPGRDPACFARGWRLDRVYGTCFCDQACRFTG
  DCCFDYDRACPARPCFVGEWSPWSGCADQCKPTTRVRRRSVQQEPQNGGAPCPPLEERAG
  CLEYSTPQGQDCGHTYVPAFITTSAFNKERTRQATSPHWSTHTEDAGYCMEFKTESLTPH
  CALENWPLTRWMQYLREGYTVCVDCQPPAMNSVSLRCSGDGLDSDGNQTLHWQAIGNPRC
  QGTWKKVRRVDQCSCPAVHSFIFI
• Tissue Specificity: Detected in aorta extracellular matrix (at protein level).
• Reactome Pathway:
  O-glycosylation of TSR domain-containing proteins (R-HSA-5173214)
  Defective B3GALTL causes PpS (R-HSA-5083635)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Crohn disease	DIS2C5Q8	moderate	Genetic Variation	[2]

8 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 Somatomedin-B and thrombospondin type-1 domain-containing protein (SBSPON).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Somatomedin-B and thrombospondin type-1 domain-containing protein (SBSPON).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Somatomedin-B and thrombospondin type-1 domain-containing protein (SBSPON).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Somatomedin-B and thrombospondin type-1 domain-containing protein (SBSPON).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Somatomedin-B and thrombospondin type-1 domain-containing protein (SBSPON).	[7]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Somatomedin-B and thrombospondin type-1 domain-containing protein (SBSPON).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Somatomedin-B and thrombospondin type-1 domain-containing protein (SBSPON).	[9]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Somatomedin-B and thrombospondin type-1 domain-containing protein (SBSPON).	[11]

2 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 Somatomedin-B and thrombospondin type-1 domain-containing protein (SBSPON).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Somatomedin-B and thrombospondin type-1 domain-containing protein (SBSPON).	[12]

References

• [1] Dpy-19 like 3-mediated C-mannosylation and expression levels of RPE-spondin in human tumor cell lines.Oncol Lett. 2017 Aug;14(2):2537-2544. doi: 10.3892/ol.2017.6465. Epub 2017 Jun 22.
• [2] A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci.PLoS Genet. 2012;8(3):e1002559. doi: 10.1371/journal.pgen.1002559. Epub 2012 Mar 8.
• [3] 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.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders. J Mol Endocrinol. 2015 Jun;54(3):289-303.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [9] 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.
• [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] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [12] 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.