Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1TYNDN)

• DOT Name: Dentin sialophosphoprotein (DSPP)
• Gene Name: DSPP
• Related Disease:
  Deafness, autosomal dominant 39, with dentinogenesis imperfecta 1
  Dentinogenesis imperfecta
  Dentinogenesis imperfecta type 2
  Rheumatoid arthritis
  Type-1 diabetes
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Bullous pemphigoid
  Chronic kidney disease
  Deafness
  Dementia
  Dental caries
  Dentinogenesis imperfecta type 3
  Diabetic kidney disease
  Glioma
  Head and neck cancer
  Head and neck carcinoma
  Kidney failure
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Multiple sclerosis
  Myocardial infarction
  Neoplasm
  Non-alcoholic fatty liver disease
  Non-small-cell lung cancer
  Oral cancer
  Osteoporosis
  Pancreatitis
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Squamous cell carcinoma
  Stroke
  Tuberculosis
  Advanced cancer
  Bone osteosarcoma
  Head-neck squamous cell carcinoma
  Osteosarcoma
  Type-1/2 diabetes
  Dentin dysplasia type I
  Dentin dysplasia type II
  Ankylosing spondylitis
  Dentin dysplasia
• UniProt ID: DSPP_HUMAN
• Sequence:
  MKIITYFCIWAVAWAIPVPQSKPLERHVEKSMNLHLLARSNVSVQDELNASGTIKESGVL
  VHEGDRGRQENTQDGHKGEGNGSKWAEVGGKSFSTYSTLANEEGNIEGWNGDTGKAETYG
  HDGIHGKEENITANGIQGQVSIIDNAGATNRSNTNGNTDKNTQNGDVGDAGHNEDVAVVQ
  EDGPQVAGSNNSTDNEDEIIENSCRNEGNTSEITPQINSKRNGTKEAEVTPGTGEDAGLD
  NSDGSPSGNGADEDEDEGSGDDEDEEAGNGKDSSNNSKGQEGQDHGKEDDHDSSIGQNSD
  SKEYYDPEGKEDPHNEVDGDKTSKSEENSAGIPEDNGSQRIEDTQKLNHRESKRVENRIT
  KESETHAVGKSQDKGIEIKGPSSGNRNITKEVGKGNEGKEDKGQHGMILGKGNVKTQGEV
  VNIEGPGQKSEPGNKVGHSNTGSDSNSDGYDSYDFDDKSMQGDDPNSSDESNGNDDANSE
  SDNNSSSRGDASYNSDESKDNGNGSDSKGAEDDDSDSTSDTNNSDSNGNGNNGNDDNDKS
  DSGKGKSDSSDSDSSDSSNSSDSSDSSDSDSSDSNSSSDSDSSDSDSSDSSDSDSSDSSN
  SSDSSDSSDSSDSSDSSDSSDSKSDSSKSESDSSDSDSKSDSSDSNSSDSSDNSDSSDSS
  NSSNSSDSSDSSDSSDSSSSSDSSNSSDSSDSSDSSNSSESSDSSDSSDSDSSDSSDSSN
  SNSSDSDSSNSSDSSDSSNSSDSSDSSDSSNSSDSSDSSDSSNSSDSSDSSDSSDSSDSS
  NSSDSNDSSNSSDSSDSSNSSDSSNSSDSSDSSDSSDSDSSNSSDSSNSSDSSDSSNSSD
  SSDSSDSSDGSDSDSSNRSDSSNSSDSSDSSDSSNSSDSSDSSDSNESSNSSDSSDSSNS
  SDSDSSDSSNSSDSSDSSNSSDSSESSNSSDNSNSSDSSNSSDSSDSSDSSNSSDSSNSS
  DSSNSSDSSDSNSSDSSDSSNSSDSSDSSDSSDSSDSSDSSNSSDSSDSSDSSDSSNSSD
  SSNSSDSSNSSDSSDSSDSSDSSDSSDSSDSSDSSNSSDSSDSSDSSDSSDSSDSSDSSD
  SSESSDSSDSSNSSDSSDSSDSSDSSDSSDSSDSSDSSDSSNSSDSSDSSDSSDSSDSSN
  SSDSSDSSESSDSSDSSDSSDSSDSSDSSDSSDSSDSSNSSDSSDSSDSSDSSDSSDSSD
  SSDSSDSSDSSDSSDSSDSSDSSDSSDSSDSNESSDSSDSSDSSDSSNSSDSSDSSDSSD
  STSDSNDESDSQSKSGNGNNNGSDSDSDSEGSDSNHSTSDD
• Function: DSP may be an important factor in dentinogenesis. DPP may bind high amount of calcium and facilitate initial mineralization of dentin matrix collagen as well as regulate the size and shape of the crystals.
• Tissue Specificity: Expressed in teeth. DPP is synthesized by odontoblast and transiently expressed by pre-ameloblasts.
• KEGG Pathway: ECM-receptor interaction (hsa04512)
• Reactome Pathway: ECM proteoglycans (R-HSA-3000178)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Deafness, autosomal dominant 39, with dentinogenesis imperfecta 1	DISH1VZH	Definitive	Autosomal dominant	[1]
Dentinogenesis imperfecta	DISJLZU4	Definitive	Autosomal dominant	[2]
Dentinogenesis imperfecta type 2	DISPKTBC	Definitive	Autosomal dominant	[3]
Rheumatoid arthritis	DISTSB4J	Definitive	Genetic Variation	[4]
Type-1 diabetes	DIS7HLUB	Definitive	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[6]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[7]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[7]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[8]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[9]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[9]
Bullous pemphigoid	DISOJLKV	Strong	Genetic Variation	[10]
Chronic kidney disease	DISW82R7	Strong	Genetic Variation	[11]
Deafness	DISKCLH4	Strong	Biomarker	[12]
Dementia	DISXL1WY	Strong	Genetic Variation	[6]
Dental caries	DISRBCMD	Strong	Biomarker	[13]
Dentinogenesis imperfecta type 3	DISO0UM8	Strong	Autosomal dominant	[14]
Diabetic kidney disease	DISJMWEY	Strong	Genetic Variation	[15]
Glioma	DIS5RPEH	Strong	Biomarker	[16]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[17]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[17]
Kidney failure	DISOVQ9P	Strong	Biomarker	[18]
Lung cancer	DISCM4YA	Strong	Biomarker	[9]
Lung carcinoma	DISTR26C	Strong	Biomarker	[9]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[19]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[20]
Myocardial infarction	DIS655KI	Strong	Biomarker	[21]
Neoplasm	DISZKGEW	Strong	Altered Expression	[22]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[23]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[24]
Oral cancer	DISLD42D	Strong	Biomarker	[25]
Osteoporosis	DISF2JE0	Strong	Biomarker	[26]
Pancreatitis	DIS0IJEF	Strong	Genetic Variation	[27]
Prostate cancer	DISF190Y	Strong	Biomarker	[28]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[28]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[29]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[30]
Stroke	DISX6UHX	Strong	Genetic Variation	[21]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[31]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[25]
Bone osteosarcoma	DIST1004	moderate	Altered Expression	[32]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[33]
Osteosarcoma	DISLQ7E2	moderate	Altered Expression	[32]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[34]
Dentin dysplasia type I	DISS0DLW	Supportive	Autosomal dominant	[35]
Dentin dysplasia type II	DISE4R1W	Supportive	Autosomal dominant	[35]
Ankylosing spondylitis	DISRC6IR	Limited	Biomarker	[36]
Dentin dysplasia	DISCGIX8	Limited	Biomarker	[37]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Dentin sialophosphoprotein (DSPP) decreases the response to substance of Cisplatin.	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dentin sialophosphoprotein (DSPP).	[38]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Dentin sialophosphoprotein (DSPP).	[39]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Dentin sialophosphoprotein (DSPP).	[40]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Dentin sialophosphoprotein (DSPP).	[41]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Dentin sialophosphoprotein (DSPP).	[42]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Dentin sialophosphoprotein (DSPP).	[43]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Dentin sialophosphoprotein (DSPP).	[44]
Glucosamine	DM4ZLFD	Approved	Glucosamine decreases the expression of Dentin sialophosphoprotein (DSPP).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Dentin sialophosphoprotein (DSPP).	[46]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Dentin sialophosphoprotein (DSPP).	[47]
Manganese	DMKT129	Investigative	Manganese increases the expression of Dentin sialophosphoprotein (DSPP).	[48]
phenamil	DMJLUFM	Investigative	phenamil increases the expression of Dentin sialophosphoprotein (DSPP).	[39]

References

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• [5] Dipeptidyl peptidase-4 inhibitors (DPP-4i) combined with vitamin D3: An exploration to treat new-onset type 1 diabetes mellitus and latent autoimmune diabetes in adults in the future.Int Immunopharmacol. 2018 Apr;57:11-17. doi: 10.1016/j.intimp.2018.02.003. Epub 2018 Feb 22.
• [6] Risk of Dementia in Older Patients with Type 2 Diabetes on Dipeptidyl-Peptidase IV Inhibitors Versus Sulfonylureas: A Real-World Population-Based Cohort Study.J Clin Med. 2018 Dec 28;8(1):28. doi: 10.3390/jcm8010028.
• [7] Combination Therapy with a Sodium-Glucose Cotransporter 2 Inhibitor and a Dipeptidyl Peptidase-4 Inhibitor Additively Suppresses Macrophage Foam Cell Formation and Atherosclerosis in Diabetic Mice.Int J Endocrinol. 2017;2017:1365209. doi: 10.1155/2017/1365209. Epub 2017 Mar 19.
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• [20] Low DPP4 expression and activity in multiple sclerosis.Clin Immunol. 2014 Feb;150(2):170-83. doi: 10.1016/j.clim.2013.11.011. Epub 2013 Nov 28.
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• [24] Norcantharidin reverses cisplatin resistance and inhibits the epithelial mesenchymal transition of human nonsmall lung cancer cells by regulating the YAP pathway.Oncol Rep. 2018 Aug;40(2):609-620. doi: 10.3892/or.2018.6486. Epub 2018 Jun 12.
• [25] DSPP-MMP20 gene silencing downregulates cancer stem cell markers in human oral cancer cells.Cell Mol Biol Lett. 2018 Jul 11;23:30. doi: 10.1186/s11658-018-0096-y. eCollection 2018.
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• [27] Nationwide Trends in Pancreatitis and Pancreatic Cancer Risk Among Patients With Newly Diagnosed Type 2 Diabetes Receiving Dipeptidyl Peptidase 4 Inhibitors.Diabetes Care. 2019 Nov;42(11):2057-2064. doi: 10.2337/dc18-2195. Epub 2019 Aug 20.
• [28] Generation and characterization of a specific single-chain antibody against DSPP as a prostate cancer biomarker: Involvement of bioinformatics-based design of novel epitopes.Int Immunopharmacol. 2019 Apr;69:217-224. doi: 10.1016/j.intimp.2019.01.016. Epub 2019 Feb 6.
• [29] Small integrin-binding proteins as serum markers for prostate cancer detection.Clin Cancer Res. 2009 Aug 15;15(16):5199-207. doi: 10.1158/1078-0432.CCR-09-0783. Epub 2009 Aug 11.
• [30] Dentin sialophosphoprotein (DSPP) gene-silencing inhibits key tumorigenic activities in human oral cancer cell line, OSC2. PLoS One. 2010 Nov 12;5(11):e13974. doi: 10.1371/journal.pone.0013974.
• [31] Tuberculosis serosurveillance and management practices of captive African elephants (Loxodonta africana) in the Kavango-Zambezi Transfrontier Conservation Area.Transbound Emerg Dis. 2018 Apr;65(2):e344-e354. doi: 10.1111/tbed.12764. Epub 2017 Nov 16.
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• [33] Effects of the novel polyphenol conjugate DPP-23 on head and neck squamous cell carcinoma cells in vitro.Oncol Lett. 2018 Jul;16(1):654-659. doi: 10.3892/ol.2018.8655. Epub 2018 May 7.
• [34] Anti-inflammatory potentials of incretin-based therapies used in the management of diabetes.Life Sci. 2020 Jan 15;241:117152. doi: 10.1016/j.lfs.2019.117152. Epub 2019 Dec 13.
• [35] Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
• [36] Antibodies Directed against a Peptide Epitope of a Klebsiella pneumoniae-Derived Protein Are Present in Ankylosing Spondylitis.PLoS One. 2017 Jan 30;12(1):e0171073. doi: 10.1371/journal.pone.0171073. eCollection 2017.
• [37] Phenotype and genotype analyses in seven families with dentinogenesis imperfecta or dentin dysplasia.Oral Dis. 2017 Apr;23(3):360-366. doi: 10.1111/odi.12621. Epub 2017 Jan 24.
• [38] Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
• [39] Stimulating effects of quercetin and phenamil on differentiation of human dental pulp cells. Eur J Oral Sci. 2013 Dec;121(6):559-65. doi: 10.1111/eos.12086. Epub 2013 Sep 17.
• [40] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [41] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [42] Investigation of in vitro odonto/osteogenic capacity of cannabidiol on human dental pulp cell. J Dent. 2021 Jun;109:103673. doi: 10.1016/j.jdent.2021.103673. Epub 2021 Apr 16.
• [43] 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.
• [44] Simvastatin induces the odontogenic differentiation of human dental pulp stem cells in vitro and in vivo. J Endod. 2009 Mar;35(3):367-72. doi: 10.1016/j.joen.2008.11.024.
• [45] Glucosamine promotes osteogenic differentiation of dental pulp stem cells through modulating the level of the transforming growth factor-beta type I receptor. J Cell Physiol. 2010 Oct;225(1):140-51.
• [46] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
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• [48] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.
• [49] Dentin sialophosphoprotein (DSPP) gene-silencing inhibits key tumorigenic activities in human oral cancer cell line, OSC2. PLoS One. 2010 Nov 12;5(11):e13974. doi: 10.1371/journal.pone.0013974.