Details of Drug Off-Target (DOT)

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

• DOT Name: Microfibrillar-associated protein 2 (MFAP2)
• Synonyms: MFAP-2; Microfibril-associated glycoprotein 1; MAGP; MAGP-1
• Gene Name: MFAP2
• Related Disease:
  Chronic obstructive pulmonary disease
  Coagulation defect
  Gastric cancer
  Head-neck squamous cell carcinoma
  Metabolic disorder
  Non-insulin dependent diabetes
  Obesity
  Stomach cancer
• UniProt ID: MFAP2_HUMAN
• Pfam ID: PF05507
• Sequence:
  MRAAYLFLLFLPAGLLAQGQYDLDPLPPFPDHVQYTHYSDQIDNPDYYDYQEVTPRPSEE
  QFQFQSQQQVQQEVIPAPTPEPGNAELEPTEPGPLDCREEQYPCTRLYSIHRPCKQCLNE
  VCFYSLRRVYVINKEICVRTVCAHEELLRADLCRDKFSKCGVMASSGLCQSVAASCARSC
  GSC
• Function: Component of the elastin-associated microfibrils.
• Reactome Pathway:
  Molecules associated with elastic fibres (R-HSA-2129379)
  Elastic fibre formation (R-HSA-1566948)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[1]
Coagulation defect	DIS9X3H6	Strong	Altered Expression	[2]
Gastric cancer	DISXGOUK	Strong	Biomarker	[3]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[3]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[4]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[5]
Obesity	DIS47Y1K	Strong	Biomarker	[3]
Stomach cancer	DISKIJSX	Strong	Biomarker	[3]

4 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 Microfibrillar-associated protein 2 (MFAP2).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Microfibrillar-associated protein 2 (MFAP2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Microfibrillar-associated protein 2 (MFAP2).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Microfibrillar-associated protein 2 (MFAP2).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Microfibrillar-associated protein 2 (MFAP2).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Microfibrillar-associated protein 2 (MFAP2).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Microfibrillar-associated protein 2 (MFAP2).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Microfibrillar-associated protein 2 (MFAP2).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Microfibrillar-associated protein 2 (MFAP2).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Microfibrillar-associated protein 2 (MFAP2).	[13]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Microfibrillar-associated protein 2 (MFAP2).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Microfibrillar-associated protein 2 (MFAP2).	[15]
Selenium	DM25CGV	Approved	Selenium increases the expression of Microfibrillar-associated protein 2 (MFAP2).	[16]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Microfibrillar-associated protein 2 (MFAP2).	[17]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Microfibrillar-associated protein 2 (MFAP2).	[7]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Microfibrillar-associated protein 2 (MFAP2).	[18]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Microfibrillar-associated protein 2 (MFAP2).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Microfibrillar-associated protein 2 (MFAP2).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Microfibrillar-associated protein 2 (MFAP2).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Microfibrillar-associated protein 2 (MFAP2).	[21]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Microfibrillar-associated protein 2 (MFAP2).	[23]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Microfibrillar-associated protein 2 (MFAP2).	[7]

References

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• [2] Deficiency in microfibril-associated glycoprotein-1 leads to complex phenotypes in multiple organ systems.J Biol Chem. 2008 Sep 12;283(37):25533-25543. doi: 10.1074/jbc.M709962200. Epub 2008 Jul 14.
• [3] MFAP2 promotes epithelial-mesenchymal transition in gastric cancer cells by activating TGF-/SMAD2/3 signaling pathway.Onco Targets Ther. 2018 Jul 12;11:4001-4017. doi: 10.2147/OTT.S160831. eCollection 2018.
• [4] Contribution of metabolic disease to bone fragility in MAGP1-deficient mice.Matrix Biol. 2018 Apr;67:1-14. doi: 10.1016/j.matbio.2018.02.022. Epub 2018 Mar 5.
• [5] Multiple genetic variations confer risks for obesity and type 2 diabetes mellitus in arab descendants from UAE.Int J Obes (Lond). 2018 Jul;42(7):1345-1353. doi: 10.1038/s41366-018-0057-6. Epub 2018 Mar 12.
• [6] 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.
• [7] Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] 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.
• [10] Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells. Toxins (Basel). 2023 Feb 9;15(2):140. doi: 10.3390/toxins15020140.
• [11] Association of Arsenic Exposure with Whole Blood DNA Methylation: An Epigenome-Wide Study of Bangladeshi Adults. Environ Health Perspect. 2019 May;127(5):57011. doi: 10.1289/EHP3849. Epub 2019 May 28.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [13] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [14] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [15] Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
• [16] 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.
• [17] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [18] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [19] 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.
• [20] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [21] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [22] 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.
• [23] 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.