Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZXH19L)

• DOT Name: Neutrophil collagenase (MMP8)
• Synonyms: EC 3.4.24.34; Matrix metalloproteinase-8; MMP-8; PMNL collagenase; PMNL-CL
• Gene Name: MMP8
• UniProt ID: MMP8_HUMAN
• PDB ID: 1A85; 1A86; 1BZS; 1I73; 1I76; 1JAN; 1JAO; 1JAP; 1JAQ; 1JH1; 1JJ9; 1KBC; 1MMB; 1MNC; 1ZP5; 1ZS0; 1ZVX; 2OY2; 2OY4; 3DNG; 3DPE; 3DPF; 3TT4; 4QKZ; 5H8X
• EC Number: 3.4.24.34
• Pfam ID: PF00045 ; PF00413 ; PF01471
• Sequence:
  MFSLKTLPFLLLLHVQISKAFPVSSKEKNTKTVQDYLEKFYQLPSNQYQSTRKNGTNVIV
  EKLKEMQRFFGLNVTGKPNEETLDMMKKPRCGVPDSGGFMLTPGNPKWERTNLTYRIRNY
  TPQLSEAEVERAIKDAFELWSVASPLIFTRISQGEADINIAFYQRDHGDNSPFDGPNGIL
  AHAFQPGQGIGGDAHFDAEETWTNTSANYNLFLVAAHEFGHSLGLAHSSDPGALMYPNYA
  FRETSNYSLPQDDIDGIQAIYGLSSNPIQPTGPSTPKPCDPSLTFDAITTLRGEILFFKD
  RYFWRRHPQLQRVEMNFISLFWPSLPTGIQAAYEDFDRDLIFLFKGNQYWALSGYDILQG
  YPKDISNYGFPSSVQAIDAAVFYRSKTYFFVNDQFWRYDNQRQFMEPGYPKSISGAFPGI
  ESKVDAVFQQEHFFHVFSGPRYYAFDLIAQRVTRVARGNKWLNCRYG
• Function: Can degrade fibrillar type I, II, and III collagens.
• Tissue Specificity: Neutrophils.
• Reactome Pathway:
  Degradation of the extracellular matrix (R-HSA-1474228)
  Activation of Matrix Metalloproteinases (R-HSA-1592389)
  Neutrophil degranulation (R-HSA-6798695)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DOT

7 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 Neutrophil collagenase (MMP8).	[1]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Neutrophil collagenase (MMP8).	[2]
Tetracycline	DMZA017	Approved	Tetracycline decreases the activity of Neutrophil collagenase (MMP8).	[3]
Doxycycline	DM7ICNU	Approved	Doxycycline decreases the activity of Neutrophil collagenase (MMP8).	[3]
Prinomastat	DM9HOKG	Approved	Prinomastat decreases the activity of Neutrophil collagenase (MMP8).	[3]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Neutrophil collagenase (MMP8).	[4]
Edetic acid	DM10D85	Investigative	Edetic acid decreases the activity of Neutrophil collagenase (MMP8).	[5]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [3] Synthesis and in vitro evaluation of targeted tetracycline derivatives: effects on inhibition of matrix metalloproteinases. Bioorg Med Chem. 2007 Mar 15;15(6):2368-74. doi: 10.1016/j.bmc.2007.01.026. Epub 2007 Jan 19.
• [4] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [5] Treatment with human metalloproteinase-8 gene delivery ameliorates experimental rat liver cirrhosis. Gastroenterology. 2004 Apr;126(4):1122-33; discussion 949. doi: 10.1053/j.gastro.2003.12.045.