Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2OR6TS)

• DOT Name: Matrix metalloproteinase-23 (MMP23B)
• Synonyms: MMP-23; EC 3.4.24.-; Femalysin; MIFR-1; Matrix metalloproteinase-21; MMP-21; Matrix metalloproteinase-22; MMP-22
• Gene Name: MMP23B
• Related Disease:
  Advanced cancer
  Bladder cancer
  Carcinoma
  Coronary atherosclerosis
  Coronary heart disease
  Esophageal squamous cell carcinoma
  HIV infectious disease
  Systemic sclerosis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Squamous cell carcinoma
  Colorectal carcinoma
  Neoplasm
• UniProt ID: MMP23_HUMAN
• EC Number: 3.4.24.-
• Pfam ID: PF00413 ; PF01549
• Sequence:
  MGRGARVPSEAPGAGVERRWLGAALVALCLLPALVLLARLGAPAVPAWSAAQGDVAALGL
  SAVPPTRVPGPLAPRRRRYTLTPARLRWDHFNLTYRILSFPRNLLSPRETRRALAAAFRM
  WSDVSPFSFREVAPEQPSDLRIGFYPINHTDCLVSALHHCFDGPTGELAHAFFPPHGGIH
  FDDSEYWVLGPTRYSWKKGVWLTDLVHVAAHEIGHALGLMHSQHGRALMHLNATLRGWKA
  LSQDELWGLHRLYGCLDRLFVCASWARRGFCDARRRLMKRLCPSSCDFCYEFPFPTVATT
  PPPPRTKTRLVPEGRNVTFRCGQKILHKKGKVYWYKDQEPLEFSYPGYLALGEAHLSIIA
  NAVNEGTYTCVVRRQQRVLTTYSWRVRVRG
• Function: Protease. May regulate the surface expression of some potassium channels by retaining them in the endoplasmic reticulum.
• Tissue Specificity: Predominantly expressed in ovary, testis and prostate.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[1]
Carcinoma	DISH9F1N	Strong	Biomarker	[2]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[3]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[4]
HIV infectious disease	DISO97HC	Strong	Genetic Variation	[5]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[6]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[1]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[7]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[8]
Neoplasm	DISZKGEW	Limited	Altered Expression	[9]

1 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-23 (MMP23B).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Matrix metalloproteinase-23 (MMP23B).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Matrix metalloproteinase-23 (MMP23B).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Matrix metalloproteinase-23 (MMP23B).	[13]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Matrix metalloproteinase-23 (MMP23B).	[14]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Matrix metalloproteinase-23 (MMP23B).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Matrix metalloproteinase-23 (MMP23B).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Matrix metalloproteinase-23 (MMP23B).	[17]

References

• [1] MMP23B expression and protein levels in blood and urine are associated with bladder cancer.Carcinogenesis. 2018 Oct 8;39(10):1254-1263. doi: 10.1093/carcin/bgy098.
• [2] Matrix metalloproteinase-21, the human orthologue for XMMP, is expressed during fetal development and in cancer.Gene. 2002 Nov 13;301(1-2):31-41. doi: 10.1016/s0378-1119(02)01088-0.
• [3] Interleukin-18, matrix metalloproteinase-22 and -29 are independent risk factors of human coronary heart disease.J Zhejiang Univ Sci B. 2017 Aug.;18(8):685-695. doi: 10.1631/jzus.B1700073.
• [4] TWIST1, MMP-21, and HLAG-1 co-overexpression is associated with ESCC aggressiveness.J Cell Biochem. 2019 Sep;120(9):14838-14846. doi: 10.1002/jcb.28745. Epub 2019 Apr 23.
• [5] Effect of matrix metalloproteinase-21 (572C/T) polymorphism on HIV-associated neurocognitive disorder.APMIS. 2018 Apr;126(4):329-336. doi: 10.1111/apm.12817.
• [6] A novel miRNA-4484 is up-regulated on microarray and associated with increased MMP-21 expression in serum of systemic sclerosis patients.Sci Rep. 2019 Oct 3;9(1):14264. doi: 10.1038/s41598-019-50695-y.
• [7] High MMP-21 expression in metastatic lymph nodes predicts unfavorable overall survival for oral squamous cell carcinoma patients with lymphatic metastasis.Oncol Rep. 2014 Jun;31(6):2644-50. doi: 10.3892/or.2014.3124. Epub 2014 Apr 2.
• [8] Identification of high-risk stage II and stage III colorectal cancer by analysis of MMP-21 expression.J Surg Oncol. 2011 Dec;104(7):787-91. doi: 10.1002/jso.21970. Epub 2011 Jun 7.
• [9] Expression of MMP-10, MMP-21, MMP-26, and MMP-28 in Merkel cell carcinoma.Virchows Arch. 2009 Dec;455(6):495-503. doi: 10.1007/s00428-009-0856-1. Epub 2009 Nov 17.
• [10] 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.
• [11] 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.
• [12] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [13] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [14] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [15] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [16] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [17] 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.