Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9O89KU)

DOT Name	Matrix metalloproteinase-26 (MMP26)
Synonyms	MMP-26; EC 3.4.24.-; Endometase; Matrilysin-2
Gene Name	MMP26
Related Disease	Narcolepsy ( ) Prostatitis ( ) Astrocytoma ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Carcinoma ( ) Endometrial carcinoma ( ) Endometrium neoplasm ( ) Esophageal squamous cell carcinoma ( ) Glioma ( ) Hepatocellular carcinoma ( ) Malaria ( ) Melanoma ( ) Neoplasm ( ) Non-small-cell lung cancer ( ) Pancreatic tumour ( ) Polycystic ovarian syndrome ( ) Prostate neoplasm ( ) Skin disease ( ) Squamous cell carcinoma ( ) Vascular purpura ( ) Lung carcinoma ( ) Advanced cancer ( ) Endometrial cancer ( ) Non-insulin dependent diabetes ( ) Prostate cancer ( ) Prostate carcinoma ( )
UniProt ID	MMP26_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	3.4.24.-
Pfam ID	PF00413
Sequence	MQLVILRVTIFLPWCFAVPVPPAADHKGWDFVEGYFHQFFLTKKESPLLTQETQTQLLQQ FHRNGTDLLDMQMHALLHQPHCGVPDGSDTSISPGRCKWNKHTLTYRIINYPHDMKPSAV KDSIYNAVSIWSNVTPLIFQQVQNGDADIKVSFWQWAHEDGWPFDGPGGILGHAFLPNSG NPGVVHFDKNEHWSASDTGYNLFLVATHEIGHSLGLQHSGNQSSIMYPTYWYHDPRTFQL SADDIQRIQHLYGEKCSSDIP
Function	May hydrolyze collagen type IV, fibronectin, fibrinogen, beta-casein, type I gelatin and alpha-1 proteinase inhibitor. Is also able to activate progelatinase B.
Tissue Specificity	Expressed specifically in uterus and placenta. Is also widely expressed in malignant tumors from different sources as well as in diverse tumor cell lines.

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Narcolepsy	DISLCNLI	Definitive	Genetic Variation	[1]
Prostatitis	DISL8OGN	Definitive	Altered Expression	[2]
Astrocytoma	DISL3V18	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	Strong	Biomarker	[4]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[5]
Endometrium neoplasm	DIS6OS2L	Strong	Biomarker	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[7]
Glioma	DIS5RPEH	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[8]
Malaria	DISQ9Y50	Strong	Genetic Variation	[9]
Melanoma	DIS1RRCY	Strong	Altered Expression	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[12]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[13]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Altered Expression	[14]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[15]
Skin disease	DISDW8R6	Strong	Biomarker	[16]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[17]
Vascular purpura	DIS6ZZMF	Strong	Altered Expression	[18]
Lung carcinoma	DISTR26C	moderate	Biomarker	[11]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[19]
Endometrial cancer	DISW0LMR	Limited	Altered Expression	[6]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[20]
Prostate cancer	DISF190Y	Limited	Biomarker	[15]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[15]
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⏷ Show the Full List of 28 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

4 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 Matrix metalloproteinase-26 (MMP26).	[16]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Matrix metalloproteinase-26 (MMP26).	[22]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Matrix metalloproteinase-26 (MMP26).	[23]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Matrix metalloproteinase-26 (MMP26).	[24]
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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 decreases the methylation of Matrix metalloproteinase-26 (MMP26).	[25]
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References

1	Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
2	Activation of pro-gelatinase B by endometase/matrilysin-2 promotes invasion of human prostate cancer cells.J Biol Chem. 2003 Apr 25;278(17):15056-64. doi: 10.1074/jbc.M210975200. Epub 2003 Feb 13.
3	High MMP-26 expression in glioma is correlated with poor clinical outcome of patients.Oncol Lett. 2018 Aug;16(2):2237-2242. doi: 10.3892/ol.2018.8880. Epub 2018 Jun 4.
4	Calcium regulates tertiary structure and enzymatic activity of human endometase/matrilysin-2 and its role in promoting human breast cancer cell invasion.Biochem J. 2007 Apr 1;403(1):31-42. doi: 10.1042/BJ20061390.
5	Estrogen and estrogen receptor induce matrix metalloproteinase-26 expression in endometrial carcinoma cells.Oncol Rep. 2013 Aug;30(2):751-6. doi: 10.3892/or.2013.2527. Epub 2013 Jun 7.
6	Matrix metalloproteinase-26 (matrilysin-2) expression is high in endometrial hyperplasia and decreases with loss of histological differentiation in endometrial cancer.Gynecol Oncol. 2004 Sep;94(3):661-70. doi: 10.1016/j.ygyno.2004.05.024.
7	Association of matrilysin-2 (MMP-26) expression with tumor progression and activation of MMP-9 in esophageal squamous cell carcinoma.Carcinogenesis. 2004 Dec;25(12):2353-60. doi: 10.1093/carcin/bgh270. Epub 2004 Aug 27.
8	Inhibition of fibroblast growth factor receptor signaling impairs metastasis of hepatocellular carcinoma.Tumour Biol. 2014 Nov;35(11):11005-11. doi: 10.1007/s13277-014-2384-0. Epub 2014 Aug 5.
9	Imputation-based meta-analysis of severe malaria in three African populations.PLoS Genet. 2013 May;9(5):e1003509. doi: 10.1371/journal.pgen.1003509. Epub 2013 May 23.
10	Identification and characterization of human endometase (Matrix metalloproteinase-26) from endometrial tumor.J Biol Chem. 2000 Jul 7;275(27):20540-4. doi: 10.1074/jbc.M002349200.
11	Non-small cell lung cancer invasion and metastasis promoted by MMP-26.Mol Med Rep. 2011 Nov-Dec;4(6):1201-9. doi: 10.3892/mmr.2011.540. Epub 2011 Jul 26.
12	Fibroblast growth factor 18 promotes proliferation and migration of H460 cells via the ERK and p38 signaling pathways.Oncol Rep. 2017 Feb;37(2):1235-1242. doi: 10.3892/or.2016.5301. Epub 2016 Dec 7.
13	Increased expression of matrix metalloproteinases-21 and -26 and TIMP-4 in pancreatic adenocarcinoma.Mod Pathol. 2007 Nov;20(11):1128-40. doi: 10.1038/modpathol.3800956. Epub 2007 Sep 14.
14	Microarray evaluation of endometrial receptivity in Chinese women with polycystic ovary syndrome.Reprod Biomed Online. 2008 Sep;17(3):425-35. doi: 10.1016/s1472-6483(10)60228-3.
15	Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor.Cell Res. 2006 Sep;16(9):750-8. doi: 10.1038/sj.cr.7310089.
16	MMP-21 is expressed by macrophages and fibroblasts in vivo and in culture. Exp Dermatol. 2006 Oct;15(10):775-83. doi: 10.1111/j.1600-0625.2006.00460.x.
17	Differential expression of matrilysin-1 (MMP-7), 92 kD gelatinase (MMP-9), and metalloelastase (MMP-12) in oral verrucous and squamous cell cancer.J Pathol. 2004 Jan;202(1):14-22. doi: 10.1002/path.1479.
18	The gene expression profile of matrix metalloproteinases and their inhibitors in children with Henoch-Schnlein purpura.Br J Dermatol. 2011 Jun;164(6):1348-55. doi: 10.1111/j.1365-2133.2011.10295.x.
19	Activation of FGF receptor signaling promotes invasion of non-small-cell lung cancer.Tumour Biol. 2015 May;36(5):3637-42. doi: 10.1007/s13277-014-3001-y. Epub 2015 Jan 8.
20	Analysis of novel risk loci for type 2 diabetes in a general French population: the D.E.S.I.R. study.J Mol Med (Berl). 2008 Mar;86(3):341-8. doi: 10.1007/s00109-007-0295-x. Epub 2008 Jan 22.
21	MMP-21 is expressed by macrophages and fibroblasts in vivo and in culture. Exp Dermatol. 2006 Oct;15(10):775-83. doi: 10.1111/j.1600-0625.2006.00460.x.
22	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.
23	Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
24	Effect of ovarian steroids on gene expression profile in human uterine microvascular endothelial cells. Fertil Steril. 2009 Aug;92(2):709-21.
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.