Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3BG37V)

• DOT Name: Matrix metalloproteinase-25 (MMP25)
• Synonyms: MMP-25; EC 3.4.24.-; Leukolysin; Membrane-type matrix metalloproteinase 6; MT-MMP 6; MTMMP6; Membrane-type-6 matrix metalloproteinase; MT6-MMP; MT6MMP
• Gene Name: MMP25
• Related Disease:
  Advanced cancer
  Amelogenesis imperfecta
  Anal intraepithelial neoplasia
  Anaplastic astrocytoma
  Brain neoplasm
  Breast carcinoma
  Carcinoma
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Fibrosarcoma
  Gastric cancer
  Glioblastoma multiforme
  Melanoma
  Meningioma
  Multiple sclerosis
  Neoplasm
  Oral cancer
  Osteoarthritis
  Plasma cell myeloma
  Stomach cancer
  Laryngeal squamous cell carcinoma
  Rheumatoid arthritis
• UniProt ID: MMP25_HUMAN
• EC Number: 3.4.24.-
• Pfam ID: PF00045 ; PF00413 ; PF01471
• Sequence:
  MRLRLRLLALLLLLLAPPARAPKPSAQDVSLGVDWLTRYGYLPPPHPAQAQLQSPEKLRD
  AIKVMQRFAGLPETGRMDPGTVATMRKPRCSLPDVLGVAGLVRRRRRYALSGSVWKKRTL
  TWRVRSFPQSSQLSQETVRVLMSYALMAWGMESGLTFHEVDSPQGQEPDILIDFARAFHQ
  DSYPFDGLGGTLAHAFFPGEHPISGDTHFDDEETWTFGSKDGEGTDLFAVAVHEFGHALG
  LGHSSAPNSIMRPFYQGPVGDPDKYRLSQDDRDGLQQLYGKAPQTPYDKPTRKPLAPPPQ
  PPASPTHSPSFPIPDRCEGNFDAIANIRGETFFFKGPWFWRLQPSGQLVSPRPARLHRFW
  EGLPAQVRVVQAAYARHRDGRILLFSGPQFWVFQDRQLEGGARPLTELGLPPGEEVDAVF
  SWPQNGKTYLVRGRQYWRYDEAAARPDPGYPRDLSLWEGAPPSPDDVTVSNAGDTYFFKG
  AHYWRFPKNSIKTEPDAPQPMGPNWLDCPAPSSGPRAPRPPKATPVSETCDCQCELNQAA
  GRWPAPIPLLLLPLLVGGVASR
• Function: May activate progelatinase A.
• Tissue Specificity: Expressed predominantly in leukocytes, lung and spleen. Expressed also in colon carcinoma, astrocytoma and glioblastomas.
• KEGG Pathway: Parathyroid hormone synthesis, secretion and action (hsa04928)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Activation of Matrix Metalloproteinases (R-HSA-1592389)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Amelogenesis imperfecta	DISGYR9E	Strong	Genetic Variation	[2]
Anal intraepithelial neoplasia	DISJ0JW3	Strong	Biomarker	[3]
Anaplastic astrocytoma	DISSBE0K	Strong	Altered Expression	[4]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Carcinoma	DISH9F1N	Strong	Biomarker	[4]
Colon cancer	DISVC52G	Strong	Altered Expression	[5]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[5]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[5]
Fibrosarcoma	DISWX7MU	Strong	Altered Expression	[1]
Gastric cancer	DISXGOUK	Strong	Biomarker	[6]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[4]
Melanoma	DIS1RRCY	Strong	Biomarker	[7]
Meningioma	DISPT4TG	Strong	Altered Expression	[4]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[9]
Oral cancer	DISLD42D	Strong	Biomarker	[3]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[10]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[11]
Stomach cancer	DISKIJSX	Strong	Biomarker	[6]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Biomarker	[12]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[13]

3 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-25 (MMP25).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Matrix metalloproteinase-25 (MMP25).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Matrix metalloproteinase-25 (MMP25).	[16]

2 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 Matrix metalloproteinase-25 (MMP25).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Matrix metalloproteinase-25 (MMP25).	[18]

References

• [1] Biochemical characterization of the cellular glycosylphosphatidylinositol-linked membrane type-6 matrix metalloproteinase.J Biol Chem. 2010 May 21;285(21):16076-86. doi: 10.1074/jbc.M110.107094. Epub 2010 Mar 22.
• [2] Homozygous and compound heterozygous MMP20 mutations in amelogenesis imperfecta.J Dent Res. 2013 Jul;92(7):598-603. doi: 10.1177/0022034513488393. Epub 2013 Apr 26.
• [3] Matrix metalloproteinase 20-dentin sialophosphoprotein interaction in oral cancer.J Dent Res. 2015 Apr;94(4):584-93. doi: 10.1177/0022034515570156. Epub 2015 Feb 9.
• [4] Human MT6-matrix metalloproteinase: identification, progelatinase A activation, and expression in brain tumors.Cancer Res. 2000 Feb 15;60(4):877-82.
• [5] MMP25 (MT6-MMP) is highly expressed in human colon cancer, promotes tumor growth, and exhibits unique biochemical properties.J Biol Chem. 2007 Jul 27;282(30):21998-2010. doi: 10.1074/jbc.M701737200. Epub 2007 May 18.
• [6] Expression of the matrix metalloproteases 2, 14, 24, and 25 and tissue inhibitor 3 as potential molecular markers in advanced human gastric cancer.Dis Markers. 2014;2014:285906. doi: 10.1155/2014/285906. Epub 2014 Feb 11.
• [7] Melanoma cell adhesion molecule is the driving force behind the dissemination of melanoma upon S100A8/A9 binding in the original skin lesion.Cancer Lett. 2019 Jun 28;452:178-190. doi: 10.1016/j.canlet.2019.03.023. Epub 2019 Mar 21.
• [8] Matrix metalloproteinase proteolysis of the myelin basic protein isoforms is a source of immunogenic peptides in autoimmune multiple sclerosis.PLoS One. 2009;4(3):e4952. doi: 10.1371/journal.pone.0004952. Epub 2009 Mar 20.
• [9] Expression Pattern of Matrix Metalloproteinase 20 (MMP20) in Human Tumors.Anticancer Res. 2016 Jun;36(6):2713-8.
• [10] Critical molecular regulators, histomorphometric indices and their correlations in the trabecular bone in primary hip osteoarthritis.Osteoarthritis Cartilage. 2010 Oct;18(10):1337-44. doi: 10.1016/j.joca.2010.07.005. Epub 2010 Aug 3.
• [11] Human beta-defensin-1 and -2 and matrix metalloproteinase-25 and -26 expression in chronic and aggressive periodontitis and in peri-implantitis.Arch Oral Biol. 2008 Feb;53(2):175-86. doi: 10.1016/j.archoralbio.2007.09.010. Epub 2007 Nov 9.
• [12] Prognostic significance of matrix metalloproteinase-20 overexpression in laryngeal squamous cell carcinoma.Acta Otolaryngol. 2011 Jul;131(7):769-73. doi: 10.3109/00016489.2011.560186. Epub 2011 Apr 5.
• [13] Analysis of 16 different matrix metalloproteinases (MMP-1 to MMP-20) in the synovial membrane: different profiles in trauma and rheumatoid arthritis.Ann Rheum Dis. 1999 Nov;58(11):691-7. doi: 10.1136/ard.58.11.691.
• [14] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [15] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [16] 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.
• [17] 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.
• [18] 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.