Details of Drug Off-Target (DOT)

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

• DOT Name: Stromelysin-3 (MMP11)
• Synonyms: SL-3; ST3; EC 3.4.24.-; Matrix metalloproteinase-11; MMP-11
• Gene Name: MMP11
• UniProt ID: MMP11_HUMAN
• EC Number: 3.4.24.-
• Pfam ID: PF00045 ; PF00413
• Sequence:
  MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDAHHLHAERRGPQPWHAALPSSPA
  PAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFPWQ
  LVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYWHGDDLPFDGPGGILAHA
  FFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFR
  YPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA
  VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQGA
  QYWVYDGEKPVLGPAPLTELGLVRFPVHAALVWGPEKNKIYFFRGRDYWRFHPSTRRVDS
  PVPRRATDWRGVPSEIDAAFQDADGYAYFLRGRLYWKFDPVKVKALEGFPRLVGPDFFGC
  AEPANTFL
• Function: May play an important role in the progression of epithelial malignancies.
• Tissue Specificity: Specifically expressed in stromal cells of breast carcinomas.
• 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

2 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 Stromelysin-3 (MMP11).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Stromelysin-3 (MMP11).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Stromelysin-3 (MMP11).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Stromelysin-3 (MMP11).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Stromelysin-3 (MMP11).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Stromelysin-3 (MMP11).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Stromelysin-3 (MMP11).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Stromelysin-3 (MMP11).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Stromelysin-3 (MMP11).	[8]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Stromelysin-3 (MMP11).	[9]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Stromelysin-3 (MMP11).	[10]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Stromelysin-3 (MMP11).	[11]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Stromelysin-3 (MMP11).	[12]
Gamolenic acid	DMQN30Z	Approved	Gamolenic acid decreases the expression of Stromelysin-3 (MMP11).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Stromelysin-3 (MMP11).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Stromelysin-3 (MMP11).	[15]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Stromelysin-3 (MMP11).	[17]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Stromelysin-3 (MMP11).	[18]
Cirsimarin	DMM10TG	Investigative	Cirsimarin decreases the expression of Stromelysin-3 (MMP11).	[19]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [9] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [10] 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.
• [11] Analysis of gene expression induced by diethylstilbestrol (DES) in human primitive Mullerian duct cells using microarray. Cancer Lett. 2005 Apr 8;220(2):197-210.
• [12] Similarities and differences between two modes of antagonism of the thyroid hormone receptor. ACS Chem Biol. 2011 Oct 21;6(10):1096-106.
• [13] Antineoplastic effects of gamma linolenic Acid on hepatocellular carcinoma cell lines. J Clin Biochem Nutr. 2010 Jul;47(1):81-90.
• [14] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [15] 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.
• [16] 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.
• [17] Acetaldehyde activates Jun/AP-1 expression and DNA binding activity in human oral keratinocytes. Oral Oncol. 2002 Apr;38(3):281-90. doi: 10.1016/s1368-8375(01)00056-2.
• [18] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.
• [19] Flavone cirsimarin impairs cell proliferation, migration, and invasion in MCF-7 cells grown in 2D and 3D models. Toxicol In Vitro. 2022 Sep;83:105416. doi: 10.1016/j.tiv.2022.105416. Epub 2022 Jun 13.