Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWLJL7K)

• DOT Name: Decorin (DCN)
• Synonyms: Bone proteoglycan II; PG-S2; PG40
• Gene Name: DCN
• Related Disease: Congenital stromal corneal dystrophy
• UniProt ID: PGS2_HUMAN
• Pfam ID: PF13855 ; PF01462
• Sequence:
  MKATIILLLLAQVSWAGPFQQRGLFDFMLEDEASGIGPEVPDDRDFEPSLGPVCPFRCQC
  HLRVVQCSDLGLDKVPKDLPPDTTLLDLQNNKITEIKDGDFKNLKNLHALILVNNKISKV
  SPGAFTPLVKLERLYLSKNQLKELPEKMPKTLQELRAHENEITKVRKVTFNGLNQMIVIE
  LGTNPLKSSGIENGAFQGMKKLSYIRIADTNITSIPQGLPPSLTELHLDGNKISRVDAAS
  LKGLNNLAKLGLSFNSISAVDNGSLANTPHLRELHLDNNKLTRVPGGLAEHKYIQVVYLH
  NNNISVVGSSDFCPPGHNTKKASYSGVSLFSNPVQYWEIQPSTFRCVYVRSAIQLGNYK
• Function: May affect the rate of fibrils formation.
• Tissue Specificity: Detected in placenta (at protein level) . Detected in cerebrospinal fluid, fibroblasts and urine (at protein level) .
• KEGG Pathway:
  TGF-beta sig.ling pathway (hsa04350)
  Cytoskeleton in muscle cells (hsa04820)
  Proteoglycans in cancer (hsa05205)
• Reactome Pathway:
  A tetrasaccharide linker sequence is required for GAG synthesis (R-HSA-1971475)
  Chondroitin sulfate biosynthesis (R-HSA-2022870)
  Dermatan sulfate biosynthesis (R-HSA-2022923)
  CS/DS degradation (R-HSA-2024101)
  ECM proteoglycans (R-HSA-3000178)
  Defective B4GALT7 causes EDS, progeroid type (R-HSA-3560783)
  Defective B3GAT3 causes JDSSDHD (R-HSA-3560801)
  Defective CHST3 causes SEDCJD (R-HSA-3595172)
  Defective CHST14 causes EDS, musculocontractural type (R-HSA-3595174)
  Defective CHSY1 causes TPBS (R-HSA-3595177)
  Defective B3GALT6 causes EDSP2 and SEMDJL1 (R-HSA-4420332)
  Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital stromal corneal dystrophy	DIS9JV4P	Definitive	Autosomal dominant	[1]

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Decorin (DCN) decreases the response to substance of Doxorubicin.	[27]
Cisplatin	DMRHGI9	Approved	Decorin (DCN) decreases the response to substance of Cisplatin.	[27]
Methotrexate	DM2TEOL	Approved	Decorin (DCN) decreases the response to substance of Methotrexate.	[27]
Paclitaxel	DMLB81S	Approved	Decorin (DCN) decreases the response to substance of Paclitaxel.	[27]
Topotecan	DMP6G8T	Approved	Decorin (DCN) decreases the response to substance of Topotecan.	[27]

25 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 Decorin (DCN).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Decorin (DCN).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Decorin (DCN).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Decorin (DCN).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Decorin (DCN).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Decorin (DCN).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Decorin (DCN).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Decorin (DCN).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Decorin (DCN).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Decorin (DCN).	[11]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Decorin (DCN).	[12]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Decorin (DCN).	[13]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Decorin (DCN).	[14]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Decorin (DCN).	[15]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Decorin (DCN).	[15]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Decorin (DCN).	[16]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Decorin (DCN).	[17]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Decorin (DCN).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Decorin (DCN).	[19]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Decorin (DCN).	[20]
Benzylpenicillin	DMS9503	Phase 3	Benzylpenicillin decreases the expression of Decorin (DCN).	[21]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Decorin (DCN).	[22]
ACYLINE	DM9GRTK	Phase 2	ACYLINE decreases the expression of Decorin (DCN).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Decorin (DCN).	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Decorin (DCN).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Decorin (DCN).	[25]

References

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• [12] Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study. J Nutr Sci. 2016 Apr 26;5:e17. doi: 10.1017/jns.2016.8. eCollection 2016.
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• [19] 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.
• [20] Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis. Mol Cell Biochem. 2011 Nov;357(1-2):83-94. doi: 10.1007/s11010-011-0878-2. Epub 2011 May 19.
• [21] Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
• [22] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [23] Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 2007 May 15;67(10):5033-41.
• [24] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [25] 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.
• [26] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
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