Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9EJ5H8)

DOT Name	Fibromodulin (FMOD)
Synonyms	FM; Collagen-binding 59 kDa protein; Keratan sulfate proteoglycan fibromodulin; KSPG fibromodulin
Gene Name	FMOD
Related Disease	leukaemia ( ) Leukemia ( ) Adult lymphoma ( ) Adult teratoma ( ) Advanced cancer ( ) Age-related macular degeneration ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Breast cancer ( ) Breast carcinoma ( ) Cardiac failure ( ) Colon carcinoma ( ) Congestive heart failure ( ) Glioblastoma multiforme ( ) Glioma ( ) Liver cirrhosis ( ) Lymphoma ( ) Metastatic prostate carcinoma ( ) Osteoarthritis ( ) Pediatric lymphoma ( ) Prostate cancer ( ) Prostate carcinoma ( ) Prostate disease ( ) Small lymphocytic lymphoma ( ) Tendinitis ( ) Teratoma ( ) B-cell neoplasm ( ) Small-cell lung cancer ( ) Chronic pancreatitis ( ) Nephropathy ( ) Adult glioblastoma ( ) Leiomyoma ( ) Neoplasm ( ) Proliferative vitreoretinopathy ( ) Uterine fibroids ( )
UniProt ID	FMOD_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	5MX0
Pfam ID	PF00560 ; PF13516 ; PF13855 ; PF01462
Sequence	MQWTSLLLLAGLFSLSQAQYEDDPHWWFHYLRSQQSTYYDPYDPYPYETYEPYPYGVDEG PAYTYGSPSPPDPRDCPQECDCPPNFPTAMYCDNRNLKYLPFVPSRMKYVYFQNNQITSI QEGVFDNATGLLWIALHGNQITSDKVGRKVFSKLRHLERLYLDHNNLTRMPGPLPRSLRE LHLDHNQISRVPNNALEGLENLTALYLQHNEIQEVGSSMRGLRSLILLDLSYNHLRKVPD GLPSALEQLYMEHNNVYTVPDSYFRGAPKLLYVRLSHNSLTNNGLASNTFNSSSLLELDL SYNQLQKIPPVNTNLENLYLQGNRINEFSISSFCTVVDVVNFSKLQVLRLDGNEIKRSAM PADAPLCLRLASLIEI
Function	Affects the rate of fibrils formation. May have a primary role in collagen fibrillogenesis.
KEGG Pathway	TGF-beta sig.ling pathway (hsa04350 )
Reactome Pathway	Keratan sulfate degradation (R-HSA-2022857 ) ECM proteoglycans (R-HSA-3000178 ) 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

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
leukaemia	DISS7D1V	Definitive	Biomarker	[1]
Leukemia	DISNAKFL	Definitive	Biomarker	[1]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[2]
Adult teratoma	DISBY81U	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[5]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[6]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Cardiac failure	DISDC067	Strong	Altered Expression	[7]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[8]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[7]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[9]
Glioma	DIS5RPEH	Strong	Biomarker	[10]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[11]
Lymphoma	DISN6V4S	Strong	Biomarker	[2]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Biomarker	[12]
Osteoarthritis	DIS05URM	Strong	Biomarker	[13]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]
Prostate disease	DISFVG19	Strong	Altered Expression	[14]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[15]
Tendinitis	DISS7ANY	Strong	Biomarker	[16]
Teratoma	DIS6ICY4	Strong	Biomarker	[3]
B-cell neoplasm	DISVY326	moderate	Genetic Variation	[17]
Small-cell lung cancer	DISK3LZD	moderate	Altered Expression	[18]
Chronic pancreatitis	DISBUOMJ	Disputed	Altered Expression	[19]
Nephropathy	DISXWP4P	Disputed	Biomarker	[20]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[9]
Leiomyoma	DISLDDFN	Limited	Biomarker	[2]
Neoplasm	DISZKGEW	Limited	Biomarker	[8]
Proliferative vitreoretinopathy	DISZTEK1	Limited	Biomarker	[21]
Uterine fibroids	DISBZRMJ	Limited	Biomarker	[2]
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⏷ Show the Full List of 35 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Fibromodulin (FMOD) affects the response to substance of Cisplatin.	[32]
Methotrexate	DM2TEOL	Approved	Fibromodulin (FMOD) affects the response to substance of Methotrexate.	[32]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Fibromodulin (FMOD).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Fibromodulin (FMOD).	[23]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Fibromodulin (FMOD).	[24]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Fibromodulin (FMOD).	[25]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Fibromodulin (FMOD).	[26]
Diazepam	DM08E9O	Approved	Diazepam decreases the expression of Fibromodulin (FMOD).	[27]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Fibromodulin (FMOD).	[28]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Fibromodulin (FMOD).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Fibromodulin (FMOD).	[31]
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⏷ Show the Full List of 9 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Fibromodulin (FMOD).	[30]
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References

1	The small leucine rich proteoglycan fibromodulin is overexpressed in human prostate epithelial cancer cell lines in culture and human prostate cancer tissue.Cancer Biomark. 2016;16(1):191-202. doi: 10.3233/CBM-150555.
2	The role of fibromodulin in cancer pathogenesis: implications for diagnosis and therapy.Cancer Cell Int. 2019 Jun 10;19:157. doi: 10.1186/s12935-019-0870-6. eCollection 2019.
3	CDKN2B upregulation prevents teratoma formation in multipotent fibromodulin-reprogrammed cells.J Clin Invest. 2019 Jul 15;129(8):3236-3251. doi: 10.1172/JCI125015. eCollection 2019 Jul 15.
4	Wnt/-Catenin Pathway-Regulated Fibromodulin Expression Is Crucial for Breast Cancer Metastasis and Inhibited by Aspirin.Front Pharmacol. 2019 Nov 25;10:1308. doi: 10.3389/fphar.2019.01308. eCollection 2019.
5	The factor H variant associated with age-related macular degeneration (His-384) and the non-disease-associated form bind differentially to C-reactive protein, fibromodulin, DNA, and necrotic cells.J Biol Chem. 2007 Apr 13;282(15):10894-900. doi: 10.1074/jbc.M610256200. Epub 2007 Feb 9.
6	Adenovirus-mediated gene transfer of fibromodulin inhibits neointimal hyperplasia in an organ culture model of human saphenous vein graft disease.Gene Ther. 2009 Sep;16(9):1154-62. doi: 10.1038/gt.2009.63. Epub 2009 May 28.
7	The extracellular matrix proteoglycan fibromodulin is upregulated in clinical and experimental heart failure and affects cardiac remodeling.PLoS One. 2018 Jul 27;13(7):e0201422. doi: 10.1371/journal.pone.0201422. eCollection 2018.
8	Fibromodulin deficiency reduces collagen structural network but not glycosaminoglycan content in a syngeneic model of colon carcinoma.PLoS One. 2017 Aug 21;12(8):e0182973. doi: 10.1371/journal.pone.0182973. eCollection 2017.
9	Glial Cell Line-Derived Neurotrophic Factor (GDNF) Promotes Angiogenesis through the Demethylation of the Fibromodulin (FMOD) Promoter in Glioblastoma.Med Sci Monit. 2018 Sep 3;24:6137-6143. doi: 10.12659/MSM.911669.
10	Integrative functional genomic analysis identifies epigenetically regulated fibromodulin as an essential gene for glioma cell migration.Oncogene. 2017 Jan 5;36(1):71-83. doi: 10.1038/onc.2016.176. Epub 2016 May 23.
11	Fibromodulin, an oxidative stress-sensitive proteoglycan, regulates the fibrogenic response to liver injury in mice.Gastroenterology. 2012 Mar;142(3):612-621.e5. doi: 10.1053/j.gastro.2011.11.029. Epub 2011 Dec 1.
12	Fibroblast and prostate tumor cell cross-talk: fibroblast differentiation, TGF-, and extracellular matrix down-regulation.Exp Cell Res. 2010 Nov 15;316(19):3207-26. doi: 10.1016/j.yexcr.2010.08.005. Epub 2010 Aug 18.
13	Catabolism of Fibromodulin in Developmental Rudiment and Pathologic Articular Cartilage Demonstrates Novel Roles for MMP-13 and ADAMTS-4 in C-terminal Processing of SLRPs.Int J Mol Sci. 2019 Jan 29;20(3):579. doi: 10.3390/ijms20030579.
14	Gene expression profiling of prostate cancer-associated genes identifies fibromodulin as potential novel biomarker for prostate cancer.Int J Biol Markers. 2016 May 28;31(2):e153-62. doi: 10.5301/jbm.5000184.
15	A seven-gene expression panel distinguishing clonal expansions of pre-leukemic and chronic lymphocytic leukemia B cells from normal B lymphocytes.Immunol Res. 2015 Dec;63(1-3):90-100. doi: 10.1007/s12026-015-8688-3.
16	Sustained expression of proteoglycans and collagen type III/type I ratio in a calcified tendinopathy model.Rheumatology (Oxford). 2010 Feb;49(2):231-9. doi: 10.1093/rheumatology/kep384. Epub 2009 Dec 2.
17	Downregulated microRNA-340-5p promotes proliferation and inhibits apoptosis of chondrocytes in osteoarthritis mice through inhibiting the extracellular signal-regulated kinase signaling pathway by negatively targeting the FMOD gene.J Cell Physiol. 2018 Jan;234(1):927-939. doi: 10.1002/jcp.26921. Epub 2018 Aug 24.
18	Tumor angiogenesis of SCLC inhibited by decreased expression of FMOD via downregulating angiogenic factors of endothelial cells.Biomed Pharmacother. 2017 Mar;87:539-547. doi: 10.1016/j.biopha.2016.12.110. Epub 2017 Jan 9.
19	Fibromodulin is upregulated by oxidative stress through the MAPK/AP-1 pathway to promote pancreatic stellate cell activation.Pancreatology. 2020 Mar;20(2):278-287. doi: 10.1016/j.pan.2019.09.011. Epub 2019 Sep 26.
20	Small proteoglycans of normal adult human kidney: distinct expression patterns of decorin, biglycan, fibromodulin, and lumican.Kidney Int. 2000 Oct;58(4):1557-68. doi: 10.1046/j.1523-1755.2000.00317.x.
21	Knockdown of Fibromodulin Inhibits Proliferation and Migration of RPE Cell via the VEGFR2-AKT Pathway.J Ophthalmol. 2018 Sep 12;2018:5708537. doi: 10.1155/2018/5708537. eCollection 2018.
22	A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
23	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.
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	Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
26	Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts. Biochem Biophys Res Commun. 2004 Feb 13;314(3):661-6. doi: 10.1016/j.bbrc.2003.12.146.
27	Patterns of some extracellular matrix gene expression are similar in cells from cleft lip-palate patients and in human palatal fibroblasts exposed to diazepam in culture. Toxicology. 2009 Mar 4;257(1-2):10-6. doi: 10.1016/j.tox.2008.12.002. Epub 2008 Dec 9.
28	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
29	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.
30	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.
31	Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
32	Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.