Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT46VXSG)

• DOT Name: Microfibrillar-associated protein 5 (MFAP5)
• Synonyms: MFAP-5; MP25; Microfibril-associated glycoprotein 2; MAGP-2
• Gene Name: MFAP5
• Related Disease:
  Adenocarcinoma
  Advanced cancer
  Aortic aneurysm, familial thoracic 9
  Breast cancer
  Breast carcinoma
  Cervical cancer
  Cervical carcinoma
  Cholangiocarcinoma
  Colon adenocarcinoma
  Colon cancer
  Colon carcinoma
  Colon polyp
  Colonic neoplasm
  Colorectal carcinoma
  Intrahepatic cholangiocarcinoma
  Metabolic disorder
  Mucinous adenocarcinoma
  Neoplasm
  Obesity
  Polyp
  Simpson-Golabi-Behmel syndrome type 1
  Varicose veins
  Epithelial ovarian cancer
  Familial thoracic aortic aneurysm and aortic dissection
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Congenital contractural arachnodactyly
  Leukoplakia
• UniProt ID: MFAP5_HUMAN
• Pfam ID: PF05507
• Sequence:
  MSLLGPKVLLFLAAFIITSDWIPLGVNSQRGDDVTQATPETFTEDPNLVNDPATDETVLA
  VLADIAPSTDDLASLSEKNTTAECWDEKFTCTRLYSVHRPVKQCIHQLCFTSLRRMYIVN
  KEICSRLVCKEHEAMKDELCRQMAGLPPRRLRRSNYFRLPPCENVDLQRPNGL
• Function: May play a role in hematopoiesis. In the cardiovascular system, could regulate growth factors or participate in cell signaling in maintaining large vessel integrity. 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

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Aortic aneurysm, familial thoracic 9	DIS1ZA91	Strong	Autosomal dominant	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[5]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[5]
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[6]
Colon adenocarcinoma	DISDRE0J	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[1]
Colon polyp	DIS7V594	Strong	Biomarker	[1]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[8]
Metabolic disorder	DIS71G5H	Strong	Genetic Variation	[9]
Mucinous adenocarcinoma	DISKNFE8	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Obesity	DIS47Y1K	Strong	Biomarker	[10]
Polyp	DISRSLYF	Strong	Altered Expression	[1]
Simpson-Golabi-Behmel syndrome type 1	DISYV73N	Strong	Altered Expression	[10]
Varicose veins	DISIMBN2	Strong	Biomarker	[11]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[12]
Familial thoracic aortic aneurysm and aortic dissection	DIS069FB	Moderate	Autosomal dominant	[13]
Ovarian cancer	DISZJHAP	moderate	Biomarker	[12]
Ovarian neoplasm	DISEAFTY	moderate	Biomarker	[12]
Pancreatic cancer	DISJC981	moderate	Biomarker	[14]
Congenital contractural arachnodactyly	DISOM1K7	Limited	Biomarker	[15]
Leukoplakia	DIST3QD3	Limited	Genetic Variation	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Microfibrillar-associated protein 5 (MFAP5).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Microfibrillar-associated protein 5 (MFAP5).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Microfibrillar-associated protein 5 (MFAP5).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Microfibrillar-associated protein 5 (MFAP5).	[19]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Microfibrillar-associated protein 5 (MFAP5).	[20]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Microfibrillar-associated protein 5 (MFAP5).	[21]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Microfibrillar-associated protein 5 (MFAP5).	[22]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Microfibrillar-associated protein 5 (MFAP5).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Microfibrillar-associated protein 5 (MFAP5).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Microfibrillar-associated protein 5 (MFAP5).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Microfibrillar-associated protein 5 (MFAP5).	[27]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Microfibrillar-associated protein 5 (MFAP5).	[28]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Microfibrillar-associated protein 5 (MFAP5).	[29]

References

• [1] Loss of microfibril-associated protein 5 (MFAP5) expression in colon cancer stroma.Virchows Arch. 2020 Mar;476(3):383-390. doi: 10.1007/s00428-019-02649-y. Epub 2019 Aug 18.
• [2] Proteomic Analysis of Cancer-Associated Fibroblasts Reveals a Paracrine Role for MFAP5 in Human Oral Tongue Squamous Cell Carcinoma.J Proteome Res. 2018 Jun 1;17(6):2045-2059. doi: 10.1021/acs.jproteome.7b00925. Epub 2018 May 2.
• [3] Microfibril-associated glycoprotein 2 (MAGP2) loss of function has pleiotropic effects in vivo. J Biol Chem. 2013 Oct 4;288(40):28869-80. doi: 10.1074/jbc.M113.497727. Epub 2013 Aug 20.
• [4] Immunohistochemical Expression of Microfibrillar-associated Protein 5 (MFAP5) in Invasive Breast Carcinoma of No Special Type.Appl Immunohistochem Mol Morphol. 2019 Oct;27(9):649-657. doi: 10.1097/PAI.0000000000000686.
• [5] MFAP5 suppression inhibits migration/invasion, regulates cell cycle and induces apoptosis via promoting ROS production in cervical cancer.Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):51-58. doi: 10.1016/j.bbrc.2018.10.146. Epub 2018 Nov 16.
• [6] YAP promotes proliferation, chemoresistance, and angiogenesis in human cholangiocarcinoma through TEAD transcription factors.Hepatology. 2015 Nov;62(5):1497-510. doi: 10.1002/hep.27992. Epub 2015 Aug 25.
• [7] MAGP2, a Component of Extracellular Matrix, Is Upregulated in Colorectal Cancer and Negatively Modulated by miR-200b-3p.Technol Cancer Res Treat. 2019 Jan 1;18:1533033819870777. doi: 10.1177/1533033819870777.
• [8] MFAP5 facilitates the aggressiveness of intrahepatic Cholangiocarcinoma by activating the Notch1 signaling pathway.J Exp Clin Cancer Res. 2019 Nov 27;38(1):476. doi: 10.1186/s13046-019-1477-4.
• [9] Microfibril-associated glycoproteins MAGP-1 and MAGP-2 in disease.Matrix Biol. 2018 Oct;71-72:100-111. doi: 10.1016/j.matbio.2018.03.006. Epub 2018 Mar 7.
• [10] MFAP5 is related to obesity-associated adipose tissue and extracellular matrix remodeling and inflammation.Obesity (Silver Spring). 2015 Jul;23(7):1371-8. doi: 10.1002/oby.21103. Epub 2015 Jun 5.
• [11] DNA methylation and gene expression profiling reveal MFAP5 as a regulatory driver of extracellular matrix remodeling in varicose vein disease.Epigenomics. 2018 Aug;10(8):1103-1119. doi: 10.2217/epi-2018-0001. Epub 2018 Aug 2.
• [12] A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor: microfibril-associated glycoprotein 2.Cancer Cell. 2009 Dec 8;16(6):521-32. doi: 10.1016/j.ccr.2009.10.018.
• [13] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [14] Anticancer Immunotherapy by MFAP5 Blockade Inhibits Fibrosis and Enhances Chemosensitivity in Ovarian and Pancreatic Cancer.Clin Cancer Res. 2019 Nov 1;25(21):6417-6428. doi: 10.1158/1078-0432.CCR-19-0187. Epub 2019 Jul 22.
• [15] Angiotensin receptor blockade attenuates cholangiocarcinoma cell growth by inhibiting the oncogenic activity of Yes-associated protein.Cancer Lett. 2018 Oct 10;434:120-129. doi: 10.1016/j.canlet.2018.07.021. Epub 2018 Jul 19.
• [16] Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer.Transl Oncol. 2017 Jun;10(3):396-409. doi: 10.1016/j.tranon.2017.03.008. Epub 2017 Apr 21.
• [17] 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.
• [18] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [19] 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.
• [20] 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.
• [21] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [22] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [23] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [24] 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.
• [25] 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.
• [26] 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.
• [27] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [28] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [29] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.