Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1XF517)

• DOT Name: Matrix metalloproteinase-15 (MMP15)
• Synonyms: MMP-15; EC 3.4.24.-; Membrane-type matrix metalloproteinase 2; MT-MMP 2; MTMMP2; Membrane-type-2 matrix metalloproteinase; MT2-MMP; MT2MMP; SMCP-2
• Gene Name: MMP15
• UniProt ID: MMP15_HUMAN
• EC Number: 3.4.24.-
• Pfam ID: PF11857 ; PF00045 ; PF00413 ; PF01471
• Sequence:
  MGSDPSAPGRPGWTGSLLGDREEAARPRLLPLLLVLLGCLGLGVAAEDAEVHAENWLRLY
  GYLPQPSRHMSTMRSAQILASALAEMQRFYGIPVTGVLDEETKEWMKRPRCGVPDQFGVR
  VKANLRRRRKRYALTGRKWNNHHLTFSIQNYTEKLGWYHSMEAVRRAFRVWEQATPLVFQ
  EVPYEDIRLRRQKEADIMVLFASGFHGDSSPFDGTGGFLAHAYFPGPGLGGDTHFDADEP
  WTFSSTDLHGNNLFLVAVHELGHALGLEHSSNPNAIMAPFYQWKDVDNFKLPEDDLRGIQ
  QLYGTPDGQPQPTQPLPTVTPRRPGRPDHRPPRPPQPPPPGGKPERPPKPGPPVQPRATE
  RPDQYGPNICDGDFDTVAMLRGEMFVFKGRWFWRVRHNRVLDNYPMPIGHFWRGLPGDIS
  AAYERQDGRFVFFKGDRYWLFREANLEPGYPQPLTSYGLGIPYDRIDTAIWWEPTGHTFF
  FQEDRYWRFNEETQRGDPGYPKPISVWQGIPASPKGAFLSNDAAYTYFYKGTKYWKFDNE
  RLRMEPGYPKSILRDFMGCQEHVEPGPRWPDVARPPFNPHGGAEPGADSAEGDVGDGDGD
  FGAGVNKDGGSRVVVQMEEVARTVNVVMVLVPLLLLLCVLGLTYALVQMQRKGAPRVLLY
  CKRSLQEWV
• Function: Endopeptidase that degrades various components of the extracellular matrix. May activate progelatinase A.
• Tissue Specificity: Appeared to be synthesized preferentially in liver, placenta, testis, colon and intestine. Substantial amounts are also detected in pancreas, kidney, lung, heart and skeletal muscle.
• KEGG Pathway: Parathyroid hormone synthesis, secretion and action (hsa04928)
• Reactome Pathway:
  Degradation of the extracellular matrix (R-HSA-1474228)
  Activation of Matrix Metalloproteinases (R-HSA-1592389)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DOT

5 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 Matrix metalloproteinase-15 (MMP15).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Matrix metalloproteinase-15 (MMP15).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Matrix metalloproteinase-15 (MMP15).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Matrix metalloproteinase-15 (MMP15).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Matrix metalloproteinase-15 (MMP15).	[18]

16 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 Matrix metalloproteinase-15 (MMP15).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Matrix metalloproteinase-15 (MMP15).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Matrix metalloproteinase-15 (MMP15).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Matrix metalloproteinase-15 (MMP15).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Matrix metalloproteinase-15 (MMP15).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Matrix metalloproteinase-15 (MMP15).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Matrix metalloproteinase-15 (MMP15).	[9]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Matrix metalloproteinase-15 (MMP15).	[10]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Matrix metalloproteinase-15 (MMP15).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Matrix metalloproteinase-15 (MMP15).	[11]
Hydroquinone	DM6AVR4	Approved	Hydroquinone affects the expression of Matrix metalloproteinase-15 (MMP15).	[12]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Matrix metalloproteinase-15 (MMP15).	[13]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Matrix metalloproteinase-15 (MMP15).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Matrix metalloproteinase-15 (MMP15).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Matrix metalloproteinase-15 (MMP15).	[16]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Matrix metalloproteinase-15 (MMP15).	[19]

References

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• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Up-regulated gene expression of angiogenesis factors in post-chemotherapeutic lung cancer tissues determined by cDNA macroarray. Oncol Rep. 2002 Jul-Aug;9(4):723-8.
• [6] Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation. J Mol Endocrinol. 2004 Apr;32(2):397-414.
• [7] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [8] 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.
• [9] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [10] Inhibition of invasion and induction of apoptosis by selenium in human malignant brain tumour cells in vitro. Int J Oncol. 2007 May;30(5):1263-71.
• [11] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [12] Survival of retinal pigment epithelium after exposure to prolonged oxidative injury: a detailed gene expression and cellular analysis. Invest Ophthalmol Vis Sci. 2004 Oct;45(10):3767-77.
• [13] Genistein suppresses the invasive potential of human breast cancer cells through transcriptional regulation of metalloproteinases and their tissue inhibitors. Int J Oncol. 2005 Apr;26(4):1101-9. doi: 10.3892/ijo.26.4.1101.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [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.
• [19] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.