Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGBI74Z)

• DOT Name: Stromelysin-1 (MMP3)
• Synonyms: SL-1; EC 3.4.24.17; Matrix metalloproteinase-3; MMP-3; Transin-1
• Gene Name: MMP3
• UniProt ID: MMP3_HUMAN
• PDB ID: 1B3D ; 1B8Y ; 1BIW ; 1BM6 ; 1BQO ; 1C3I ; 1C8T ; 1CAQ ; 1CIZ ; 1CQR ; 1D5J ; 1D7X ; 1D8F ; 1D8M ; 1G05 ; 1G49 ; 1G4K ; 1HFS ; 1HY7 ; 1OO9 ; 1QIA ; 1QIC ; 1SLM ; 1SLN ; 1UEA ; 1UMS ; 1UMT ; 1USN ; 2D1O ; 2JNP ; 2JT5 ; 2JT6 ; 2SRT ; 2USN ; 3OHL ; 3OHO ; 3USN ; 4DPE ; 4G9L ; 4JA1 ; 6MAV ; 6N9D ; 7S7L ; 7S7M
• EC Number: 3.4.24.17
• Pfam ID: PF00045 ; PF00413 ; PF01471
• Sequence:
  MKSLPILLLLCVAVCSAYPLDGAARGEDTSMNLVQKYLENYYDLKKDVKQFVRRKDSGPV
  VKKIREMQKFLGLEVTGKLDSDTLEVMRKPRCGVPDVGHFRTFPGIPKWRKTHLTYRIVN
  YTPDLPKDAVDSAVEKALKVWEEVTPLTFSRLYEGEADIMISFAVREHGDFYPFDGPGNV
  LAHAYAPGPGINGDAHFDDDEQWTKDTTGTNLFLVAAHEIGHSLGLFHSANTEALMYPLY
  HSLTDLTRFRLSQDDINGIQSLYGPPPDSPETPLVPTEPVPPEPGTPANCDPALSFDAVS
  TLRGEILIFKDRHFWRKSLRKLEPELHLISSFWPSLPSGVDAAYEVTSKDLVFIFKGNQF
  WAIRGNEVRAGYPRGIHTLGFPPTVRKIDAAISDKEKNKTYFFVEDKYWRFDEKRNSMEP
  GFPKQIAEDFPGIDSKIDAVFEEFGFFYFFTGSSQLEFDPNAKKVTHTLKSNSWLNC
• Function: Metalloproteinase with a rather broad substrate specificity that can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates different molecules including growth factors, plasminogen or other matrix metalloproteinases such as MMP9. Once released into the extracellular matrix (ECM), the inactive pro-enzyme is activated by the plasmin cascade signaling pathway. Acts also intracellularly. For example, in dopaminergic neurons, gets activated by the serine protease HTRA2 upon stress and plays a pivotal role in DA neuronal degeneration by mediating microglial activation and alpha-synuclein/SNCA cleavage. In addition, plays a role in immune response and possesses antiviral activity against various viruses such as vesicular stomatitis virus, influenza A virus (H1N1) and human herpes virus 1. Mechanistically, translocates from the cytoplasm into the cell nucleus upon virus infection to influence NF-kappa-B activities.
• KEGG Pathway:
  IL-17 sig.ling pathway (hsa04657)
  TNF sig.ling pathway (hsa04668)
  Coro.virus disease - COVID-19 (hsa05171)
  Transcriptio.l misregulation in cancer (hsa05202)
  Prostate cancer (hsa05215)
  Rheumatoid arthritis (hsa05323)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Degradation of the extracellular matrix (R-HSA-1474228)
  Activation of Matrix Metalloproteinases (R-HSA-1592389)
  Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)
  EGFR Transactivation by Gastrin (R-HSA-2179392)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Simvastatin	DM30SGU	Approved	Stromelysin-1 (MMP3) increases the Acute myocardial infarction ADR of Simvastatin.	[44]
Pravastatin	DM6A0X7	Approved	Stromelysin-1 (MMP3) increases the Acute myocardial infarction ADR of Pravastatin.	[44]
Fluvastatin	DM4MDJY	Approved	Stromelysin-1 (MMP3) increases the Acute myocardial infarction ADR of Fluvastatin.	[44]
Atorvastatin	DMF28YC	Phase 3 Trial	Stromelysin-1 (MMP3) increases the Acute myocardial infarction ADR of Atorvastatin.	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Stromelysin-1 (MMP3).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Stromelysin-1 (MMP3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Stromelysin-1 (MMP3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Stromelysin-1 (MMP3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Stromelysin-1 (MMP3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Stromelysin-1 (MMP3).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Stromelysin-1 (MMP3).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Stromelysin-1 (MMP3).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Stromelysin-1 (MMP3).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Stromelysin-1 (MMP3).	[10]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Stromelysin-1 (MMP3).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Stromelysin-1 (MMP3).	[12]
Marinol	DM70IK5	Approved	Marinol increases the expression of Stromelysin-1 (MMP3).	[13]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Stromelysin-1 (MMP3).	[14]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Stromelysin-1 (MMP3).	[11]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Stromelysin-1 (MMP3).	[15]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Stromelysin-1 (MMP3).	[17]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Stromelysin-1 (MMP3).	[18]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Stromelysin-1 (MMP3).	[19]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Stromelysin-1 (MMP3).	[20]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Stromelysin-1 (MMP3).	[21]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Stromelysin-1 (MMP3).	[22]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Stromelysin-1 (MMP3).	[23]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Stromelysin-1 (MMP3).	[25]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Stromelysin-1 (MMP3).	[26]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Stromelysin-1 (MMP3).	[27]
Rofecoxib	DM3P5DA	Approved	Rofecoxib increases the expression of Stromelysin-1 (MMP3).	[26]
Glucosamine	DM4ZLFD	Approved	Glucosamine decreases the expression of Stromelysin-1 (MMP3).	[28]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the expression of Stromelysin-1 (MMP3).	[29]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR increases the expression of Stromelysin-1 (MMP3).	[30]
Tetracycline	DMZA017	Approved	Tetracycline decreases the activity of Stromelysin-1 (MMP3).	[31]
Chloramphenicol	DMFXEWT	Approved	Chloramphenicol increases the expression of Stromelysin-1 (MMP3).	[32]
Doxycycline	DM7ICNU	Approved	Doxycycline decreases the activity of Stromelysin-1 (MMP3).	[31]
Aminolevulinic acid hci	DMS4BLQ	Approved	Aminolevulinic acid hci affects the expression of Stromelysin-1 (MMP3).	[33]
Prinomastat	DM9HOKG	Approved	Prinomastat decreases the activity of Stromelysin-1 (MMP3).	[31]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Stromelysin-1 (MMP3).	[34]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Stromelysin-1 (MMP3).	[9]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Stromelysin-1 (MMP3).	[35]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Stromelysin-1 (MMP3).	[36]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Stromelysin-1 (MMP3).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Stromelysin-1 (MMP3).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Stromelysin-1 (MMP3).	[39]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Stromelysin-1 (MMP3).	[40]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Stromelysin-1 (MMP3).	[21]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Stromelysin-1 (MMP3).	[21]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Stromelysin-1 (MMP3).	[21]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of Stromelysin-1 (MMP3).	[41]
Farnesol	DMV2X1B	Investigative	Farnesol increases the expression of Stromelysin-1 (MMP3).	[21]
Isoarnebin 4	DM0B7NO	Investigative	Isoarnebin 4 decreases the expression of Stromelysin-1 (MMP3).	[42]
DIECKOL	DMBCK4G	Investigative	DIECKOL decreases the expression of Stromelysin-1 (MMP3).	[43]
Anandamide	DMCKH3P	Investigative	Anandamide increases the expression of Stromelysin-1 (MMP3).	[13]

3 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Folic acid	DMEMBJC	Approved	Folic acid increases the secretion of Stromelysin-1 (MMP3).	[16]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the secretion of Stromelysin-1 (MMP3).	[24]
Zithromax	DMN4H2O	Approved	Zithromax decreases the secretion of Stromelysin-1 (MMP3).	[24]

1 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 Stromelysin-1 (MMP3).	[37]

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