Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKP5S4L)

• DOT Name: Mimecan (OGN)
• Synonyms: Osteoglycin; Osteoinductive factor; OIF
• Gene Name: OGN
• Related Disease:
  Lung cancer
  Non-small-cell lung cancer
  Adenoma
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Cardiovascular disease
  Cervical carcinoma
  Chronic kidney disease
  Colorectal adenoma
  Colorectal carcinoma
  Congestive heart failure
  Coronary heart disease
  Diabetic kidney disease
  Essential hypertension
  High blood pressure
  Hyperlipidemia
  Major depressive disorder
  Myocardial infarction
  Neoplasm
  Osteoporosis
  Post-traumatic stress disorder
  Type-1/2 diabetes
  Brain neoplasm
  Meningioma
  Non-insulin dependent diabetes
  Thyroid gland follicular carcinoma
  Aortic valve stenosis
  Glaucoma/ocular hypertension
  OPTN-related open angle glaucoma
• UniProt ID: MIME_HUMAN
• Pfam ID: PF13855
• Sequence:
  MKTLQSTLLLLLLVPLIKPAPPTQQDSRIIYDYGTDNFEESIFSQDYEDKYLDGKNIKEK
  ETVIIPNEKSLQLQKDEAITPLPPKKENDEMPTCLLCVCLSGSVYCEEVDIDAVPPLPKE
  SAYLYARFNKIKKLTAKDFADIPNLRRLDFTGNLIEDIEDGTFSKLSLLEELSLAENQLL
  KLPVLPPKLTLFNAKYNKIKSRGIKANAFKKLNNLTFLYLDHNALESVPLNLPESLRVIH
  LQFNNIASITDDTFCKANDTSYIRDRIEEIRLEGNPIVLGKHPNSFICLKRLPIGSYF
• Function: Induces bone formation in conjunction with TGF-beta-1 or TGF-beta-2.
• Tissue Specificity: Bone.
• Reactome Pathway:
  Keratan sulfate degradation (R-HSA-2022857)
  Defective CHST6 causes MCDC1 (R-HSA-3656225)
  Defective ST3GAL3 causes MCT12 and EIEE15 (R-HSA-3656243)
  Defective B4GALT1 causes B4GALT1-CDG (CDG-2d) (R-HSA-3656244)
  Keratan sulfate biosynthesis (R-HSA-2022854)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Definitive	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Biomarker	[1]
Adenoma	DIS78ZEV	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Cardiac failure	DISDC067	Strong	Biomarker	[6]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[7]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[5]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[8]
Colorectal adenoma	DISTSVHM	Strong	Altered Expression	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[9]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[6]
Coronary heart disease	DIS5OIP1	Strong	Altered Expression	[10]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[11]
Essential hypertension	DIS7WI98	Strong	Biomarker	[12]
High blood pressure	DISY2OHH	Strong	Biomarker	[13]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[14]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[14]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Osteoporosis	DISF2JE0	Strong	Biomarker	[15]
Post-traumatic stress disorder	DISHL1EY	Strong	Biomarker	[16]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[14]
Brain neoplasm	DISY3EKS	moderate	Altered Expression	[17]
Meningioma	DISPT4TG	moderate	Biomarker	[17]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Biomarker	[7]
Thyroid gland follicular carcinoma	DISFK2QT	moderate	Altered Expression	[18]
Aortic valve stenosis	DISW7AQ9	Limited	Altered Expression	[19]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Biomarker	[20]
OPTN-related open angle glaucoma	DISDR98A	Limited	Altered Expression	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mimecan (OGN).	[21]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mimecan (OGN).	[22]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Mimecan (OGN).	[23]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Mimecan (OGN).	[24]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Mimecan (OGN).	[25]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Mimecan (OGN).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Mimecan (OGN).	[27]

References

• [1] Different expression of mimecan as a marker for differential diagnosis between NSCLC and SCLC.Oncol Rep. 2009 Nov;22(5):1057-61. doi: 10.3892/or_00000536.
• [2] Differential expression of mimecan and thioredoxin domain-containing protein 5 in colorectal adenoma and cancer: a proteomic study.Exp Biol Med (Maywood). 2007 Oct;232(9):1152-9. doi: 10.3181/0701-RM-8.
• [3] Osteoglycin-induced VEGF Inhibition Enhances T Lymphocytes Infiltrating in Colorectal Cancer.EBioMedicine. 2018 Aug;34:35-45. doi: 10.1016/j.ebiom.2018.07.021. Epub 2018 Jul 21.
• [4] Cancer biomarkers in atherosclerotic plaque: Evidenced from structural and proteomic analyses.Biochem Biophys Res Commun. 2019 Feb 12;509(3):687-693. doi: 10.1016/j.bbrc.2018.12.160. Epub 2019 Jan 5.
• [5] Osteoglycin (OGN) Inhibits Cell Proliferation and Invasiveness in Breast Cancer via PI3K/Akt/mTOR Signaling Pathway.Onco Targets Ther. 2019 Dec 4;12:10639-10650. doi: 10.2147/OTT.S222967. eCollection 2019.
• [6] Osteoglycin prevents cardiac dilatation and dysfunction after myocardial infarction through infarct collagen strengthening.Circ Res. 2015 Jan 30;116(3):425-36. doi: 10.1161/CIRCRESAHA.116.304599. Epub 2014 Dec 17.
• [7] Osteoglycin and Bone-a Systematic Review.Curr Osteoporos Rep. 2019 Oct;17(5):250-255. doi: 10.1007/s11914-019-00523-z.
• [8] Higher Serum Levels of Osteoglycin Are Associated with All-Cause Mortality and Cardiovascular and Cerebrovascular Events in Patients with Advanced Chronic Kidney Disease.Tohoku J Exp Med. 2017 Aug;242(4):281-290. doi: 10.1620/tjem.242.281.
• [9] Osteoglycin (OGN) reverses epithelial to mesenchymal transition and invasiveness in colorectal cancer via EGFR/Akt pathway.J Exp Clin Cancer Res. 2018 Mar 2;37(1):41. doi: 10.1186/s13046-018-0718-2.
• [10] Low Levels of Plasma Osteoglycin in Patients with Complex Coronary Lesions.J Atheroscler Thromb. 2018 Nov 1;25(11):1149-1155. doi: 10.5551/jat.43059. Epub 2018 Mar 5.
• [11] Serum osteoinductive factor is associated with microalbuminuria and diabetic nephropathy in type 2 diabetes.Medicine (Baltimore). 2018 Aug;97(31):e11759. doi: 10.1097/MD.0000000000011759.
• [12] Association of SLRPs with carotid artery atherosclerosis in essential hypertensive patients.J Hum Hypertens. 2018 Sep;32(8-9):564-571. doi: 10.1038/s41371-018-0077-7. Epub 2018 Jun 5.
• [13] Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass.Nat Genet. 2008 May;40(5):546-52. doi: 10.1038/ng.134.
• [14] Characterization and Comparison of Physical and Mental Health Profiles and Department of Veterans Affairs Health Care Utilization Patterns among Operation Iraqi Freedom/Operation Enduring Freedom Women Veterans in Puerto Rico versus the United States.Womens Health Issues. 2020 Jan-Feb;30(1):49-56. doi: 10.1016/j.whi.2019.10.004. Epub 2019 Nov 30.
• [15] Effects of Osteoglycin (OGN) on treating senile osteoporosis by regulating MSCs.BMC Musculoskelet Disord. 2017 Oct 26;18(1):423. doi: 10.1186/s12891-017-1779-7.
• [16] Ketamine Administration During Hospitalization Is Not Associated With Posttraumatic Stress Disorder Outcomes in Military Combat Casualties: A Matched Cohort Study.Anesth Analg. 2020 Feb;130(2):402-408. doi: 10.1213/ANE.0000000000004327.
• [17] Osteoglycin promotes meningioma development through downregulation of NF2 and activation of mTOR signaling.Cell Commun Signal. 2017 Sep 18;15(1):34. doi: 10.1186/s12964-017-0189-7.
• [18] Molecular differences between human thyroid follicular adenoma and carcinoma revealed by analysis of a murine model of thyroid cancer.Endocrinology. 2013 Sep;154(9):3043-53. doi: 10.1210/en.2013-1028. Epub 2013 Jun 10.
• [19] Osteoglycin prevents the development of age-related diastolic dysfunction during pressure overload by reducing cardiac fibrosis and inflammation.Matrix Biol. 2018 Mar;66:110-124. doi: 10.1016/j.matbio.2017.09.002. Epub 2017 Sep 25.
• [20] Detection of differentially expressed glycogenes in trabecular meshwork of eyes with primary open-angle glaucoma.Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1491-9. doi: 10.1167/iovs.05-0736.
• [21] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
• [22] 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.
• [23] Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders. J Mol Endocrinol. 2015 Jun;54(3):289-303.
• [24] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [25] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [26] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [27] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.