Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5NIWA2)

DOT Name 72 kDa type IV collagenase (MMP2)
Synonyms EC 3.4.24.24; 72 kDa gelatinase; Gelatinase A; Matrix metalloproteinase-2; MMP-2; TBE-1
Gene Name MMP2
Related Disease
Winchester syndrome ( )
Multicentric osteolysis, nodulosis, and arthropathy ( )
Multicentric osteolysis-nodulosis-arthropathy spectrum ( )
UniProt ID
MMP2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1CK7; 1CXW; 1EAK; 1GEN; 1GXD; 1HOV; 1J7M; 1KS0; 1QIB; 1RTG; 3AYU; 7XGJ; 7XJO; 8H78
EC Number
3.4.24.24
Pfam ID
PF00040 ; PF00045 ; PF00413
Sequence
MEALMARGALTGPLRALCLLGCLLSHAAAAPSPIIKFPGDVAPKTDKELAVQYLNTFYGC
PKESCNLFVLKDTLKKMQKFFGLPQTGDLDQNTIETMRKPRCGNPDVANYNFFPRKPKWD
KNQITYRIIGYTPDLDPETVDDAFARAFQVWSDVTPLRFSRIHDGEADIMINFGRWEHGD
GYPFDGKDGLLAHAFAPGTGVGGDSHFDDDELWTLGEGQVVRVKYGNADGEYCKFPFLFN
GKEYNSCTDTGRSDGFLWCSTTYNFEKDGKYGFCPHEALFTMGGNAEGQPCKFPFRFQGT
SYDSCTTEGRTDGYRWCGTTEDYDRDKKYGFCPETAMSTVGGNSEGAPCVFPFTFLGNKY
ESCTSAGRSDGKMWCATTANYDDDRKWGFCPDQGYSLFLVAAHEFGHAMGLEHSQDPGAL
MAPIYTYTKNFRLSQDDIKGIQELYGASPDIDLGTGPTPTLGPVTPEICKQDIVFDGIAQ
IRGEIFFFKDRFIWRTVTPRDKPMGPLLVATFWPELPEKIDAVYEAPQEEKAVFFAGNEY
WIYSASTLERGYPKPLTSLGLPPDVQRVDAAFNWSKNKKTYIFAGDKFWRYNEVKKKMDP
GFPKLIADAWNAIPDNLDAVVDLQGGGHSYFFKGAYYLKLENQSLKSVKFGSIKSDWLGC
Function
Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14.; PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.; [Isoform 2]: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.
Tissue Specificity Produced by normal skin fibroblasts. PEX is expressed in a number of tumors including gliomas, breast and prostate.
KEGG Pathway
Endocrine resistance (hsa01522 )
Leukocyte transendothelial migration (hsa04670 )
GnRH sig.ling pathway (hsa04912 )
Estrogen sig.ling pathway (hsa04915 )
Relaxin sig.ling pathway (hsa04926 )
AGE-RAGE sig.ling pathway in diabetic complications (hsa04933 )
Pathways in cancer (hsa05200 )
Proteoglycans in cancer (hsa05205 )
Bladder cancer (hsa05219 )
Diabetic cardiomyopathy (hsa05415 )
Fluid shear stress and atherosclerosis (hsa05418 )
Reactome Pathway
Degradation of the extracellular matrix (R-HSA-1474228 )
Activation of Matrix Metalloproteinases (R-HSA-1592389 )
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426 )
EPH-ephrin mediated repulsion of cells (R-HSA-3928665 )
Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807 )
Extra-nuclear estrogen signaling (R-HSA-9009391 )
Collagen degradation (R-HSA-1442490 )
BioCyc Pathway
MetaCyc:HS01565-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Winchester syndrome DISS4AF5 Definitive Autosomal recessive [1]
Multicentric osteolysis, nodulosis, and arthropathy DISFX8HF Strong Autosomal recessive [2]
Multicentric osteolysis-nodulosis-arthropathy spectrum DISG2NHG Supportive Autosomal recessive [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 72 kDa type IV collagenase (MMP2). [4]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of 72 kDa type IV collagenase (MMP2). [73]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of 72 kDa type IV collagenase (MMP2). [87]
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92 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of 72 kDa type IV collagenase (MMP2). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of 72 kDa type IV collagenase (MMP2). [6]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of 72 kDa type IV collagenase (MMP2). [7]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of 72 kDa type IV collagenase (MMP2). [8]
Arsenic DMTL2Y1 Approved Arsenic increases the expression of 72 kDa type IV collagenase (MMP2). [9]
Quercetin DM3NC4M Approved Quercetin decreases the expression of 72 kDa type IV collagenase (MMP2). [10]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of 72 kDa type IV collagenase (MMP2). [11]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of 72 kDa type IV collagenase (MMP2). [12]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of 72 kDa type IV collagenase (MMP2). [13]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of 72 kDa type IV collagenase (MMP2). [14]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of 72 kDa type IV collagenase (MMP2). [15]
Triclosan DMZUR4N Approved Triclosan increases the expression of 72 kDa type IV collagenase (MMP2). [16]
Marinol DM70IK5 Approved Marinol decreases the expression of 72 kDa type IV collagenase (MMP2). [17]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of 72 kDa type IV collagenase (MMP2). [18]
Selenium DM25CGV Approved Selenium decreases the expression of 72 kDa type IV collagenase (MMP2). [19]
Progesterone DMUY35B Approved Progesterone decreases the expression of 72 kDa type IV collagenase (MMP2). [20]
Menadione DMSJDTY Approved Menadione decreases the expression of 72 kDa type IV collagenase (MMP2). [21]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of 72 kDa type IV collagenase (MMP2). [22]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of 72 kDa type IV collagenase (MMP2). [24]
Isotretinoin DM4QTBN Approved Isotretinoin increases the expression of 72 kDa type IV collagenase (MMP2). [25]
Troglitazone DM3VFPD Approved Troglitazone decreases the activity of 72 kDa type IV collagenase (MMP2). [26]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the activity of 72 kDa type IV collagenase (MMP2). [27]
Nicotine DMWX5CO Approved Nicotine increases the expression of 72 kDa type IV collagenase (MMP2). [29]
Simvastatin DM30SGU Approved Simvastatin decreases the activity of 72 kDa type IV collagenase (MMP2). [30]
Fenofibrate DMFKXDY Approved Fenofibrate decreases the expression of 72 kDa type IV collagenase (MMP2). [31]
Acocantherin DM7JT24 Approved Acocantherin decreases the expression of 72 kDa type IV collagenase (MMP2). [32]
Thalidomide DM70BU5 Approved Thalidomide decreases the expression of 72 kDa type IV collagenase (MMP2). [33]
Phenytoin DMNOKBV Approved Phenytoin decreases the expression of 72 kDa type IV collagenase (MMP2). [34]
Cholecalciferol DMGU74E Approved Cholecalciferol decreases the activity of 72 kDa type IV collagenase (MMP2). [35]
Isoproterenol DMK7MEY Approved Isoproterenol increases the expression of 72 kDa type IV collagenase (MMP2). [36]
Lovastatin DM9OZWQ Approved Lovastatin decreases the expression of 72 kDa type IV collagenase (MMP2). [37]
Ardeparin DMYRX8B Approved Ardeparin decreases the activity of 72 kDa type IV collagenase (MMP2). [38]
Propofol DMB4OLE Approved Propofol decreases the expression of 72 kDa type IV collagenase (MMP2). [39]
Melatonin DMKWFBT Approved Melatonin decreases the expression of 72 kDa type IV collagenase (MMP2). [6]
Ximelegatran DMU8ANS Approved Ximelegatran decreases the expression of 72 kDa type IV collagenase (MMP2). [41]
Cantharidin DMBP5N3 Approved Cantharidin decreases the expression of 72 kDa type IV collagenase (MMP2). [42]
Tetracycline DMZA017 Approved Tetracycline decreases the activity of 72 kDa type IV collagenase (MMP2). [43]
Propranolol DM79NTF Approved Propranolol decreases the expression of 72 kDa type IV collagenase (MMP2). [44]
Sodium chloride DMM3950 Approved Sodium chloride increases the expression of 72 kDa type IV collagenase (MMP2). [45]
Norepinephrine DMOUC09 Approved Norepinephrine increases the expression of 72 kDa type IV collagenase (MMP2). [36]
Hydroxychloroquine DMSIVND Approved Hydroxychloroquine decreases the expression of 72 kDa type IV collagenase (MMP2). [46]
Sanguinarine DMDINFS Approved Sanguinarine decreases the expression of 72 kDa type IV collagenase (MMP2). [47]
Terbinafine DMI6HUW Approved Terbinafine decreases the expression of 72 kDa type IV collagenase (MMP2). [48]
Emetine DMCT2YF Approved Emetine decreases the expression of 72 kDa type IV collagenase (MMP2). [49]
Metoprolol DMOJ0V6 Approved Metoprolol decreases the expression of 72 kDa type IV collagenase (MMP2). [44]
Tetracaine DM9J6C2 Approved Tetracaine decreases the expression of 72 kDa type IV collagenase (MMP2). [50]
Doxycycline DM7ICNU Approved Doxycycline decreases the activity of 72 kDa type IV collagenase (MMP2). [43]
Alendronate DMY2KX9 Approved Alendronate decreases the expression of 72 kDa type IV collagenase (MMP2). [51]
Prinomastat DM9HOKG Approved Prinomastat decreases the activity of 72 kDa type IV collagenase (MMP2). [43]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of 72 kDa type IV collagenase (MMP2). [52]
Berberine DMC5Q8X Phase 4 Berberine decreases the activity of 72 kDa type IV collagenase (MMP2). [53]
Glyceryl trinitrate DMF72W3 Phase 4 Glyceryl trinitrate increases the expression of 72 kDa type IV collagenase (MMP2). [54]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of 72 kDa type IV collagenase (MMP2). [56]
Curcumin DMQPH29 Phase 3 Curcumin decreases the activity of 72 kDa type IV collagenase (MMP2). [57]
Fenretinide DMRD5SP Phase 3 Fenretinide decreases the activity of 72 kDa type IV collagenase (MMP2). [58]
HMPL-004 DM29XGY Phase 3 HMPL-004 decreases the expression of 72 kDa type IV collagenase (MMP2). [59]
Chloroquine DMSI5CB Phase 3 Trial Chloroquine decreases the expression of 72 kDa type IV collagenase (MMP2). [60]
VAL-083 DM9J5Q4 Phase 3 VAL-083 decreases the expression of 72 kDa type IV collagenase (MMP2). [61]
ICI 118,551 DM3OU54 Phase 3 ICI 118,551 decreases the expression of 72 kDa type IV collagenase (MMP2). [44]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of 72 kDa type IV collagenase (MMP2). [62]
Thymoquinone DMVDTR2 Phase 2/3 Thymoquinone decreases the expression of 72 kDa type IV collagenase (MMP2). [63]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of 72 kDa type IV collagenase (MMP2). [64]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate increases the expression of 72 kDa type IV collagenase (MMP2). [65]
Disulfiram DMCL2OK Phase 2 Trial Disulfiram decreases the expression of 72 kDa type IV collagenase (MMP2). [66]
BAICALEIN DM4C7E6 Phase 2 BAICALEIN decreases the activity of 72 kDa type IV collagenase (MMP2). [67]
URSOLIC ACID DM4SOAW Phase 2 URSOLIC ACID decreases the expression of 72 kDa type IV collagenase (MMP2). [68]
LY2784544 DMZASMP Phase 2 LY2784544 decreases the expression of 72 kDa type IV collagenase (MMP2). [69]
G1 DMTV42K Phase 1/2 G1 increases the activity of 72 kDa type IV collagenase (MMP2). [70]
Taurocholic acid DM2LZ8F Phase 1/2 Taurocholic acid increases the expression of 72 kDa type IV collagenase (MMP2). [71]
PIPERINE DMYEAB1 Phase 1/2 PIPERINE decreases the expression of 72 kDa type IV collagenase (MMP2). [72]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of 72 kDa type IV collagenase (MMP2). [74]
LY294002 DMY1AFS Phase 1 LY294002 decreases the expression of 72 kDa type IV collagenase (MMP2). [75]
Sphingosine-1-Phosphate DMJCQKA Phase 1 Sphingosine-1-Phosphate increases the expression of 72 kDa type IV collagenase (MMP2). [71]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of 72 kDa type IV collagenase (MMP2). [77]
Eugenol DM7US1H Patented Eugenol decreases the expression of 72 kDa type IV collagenase (MMP2). [78]
PMID26394986-Compound-22 DM43Z1G Patented PMID26394986-Compound-22 affects the expression of 72 kDa type IV collagenase (MMP2). [79]
PMID26394986-Compound-10 DMP8RQ4 Patented PMID26394986-Compound-10 affects the expression of 72 kDa type IV collagenase (MMP2). [80]
GM6001 DM7V9CT Discontinued in Phase 2 GM6001 decreases the expression of 72 kDa type IV collagenase (MMP2). [81]
PJ34 DMXO6YH Preclinical PJ34 decreases the activity of 72 kDa type IV collagenase (MMP2). [82]
SB 203580 DMAET6F Terminated SB 203580 decreases the expression of 72 kDa type IV collagenase (MMP2). [83]
Wortmannin DM8EVK5 Terminated Wortmannin decreases the expression of 72 kDa type IV collagenase (MMP2). [83]
EMBELIN DMFZO4Y Terminated EMBELIN decreases the expression of 72 kDa type IV collagenase (MMP2). [84]
WIN-55212-2 DMACBIW Terminated WIN-55212-2 decreases the activity of 72 kDa type IV collagenase (MMP2). [85]
CP-471358 DMDEPKM Terminated CP-471358 decreases the activity of 72 kDa type IV collagenase (MMP2). [86]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of 72 kDa type IV collagenase (MMP2). [88]
Milchsaure DM462BT Investigative Milchsaure increases the expression of 72 kDa type IV collagenase (MMP2). [89]
Coumarin DM0N8ZM Investigative Coumarin decreases the expression of 72 kDa type IV collagenase (MMP2). [90]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of 72 kDa type IV collagenase (MMP2). [91]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of 72 kDa type IV collagenase (MMP2). [92]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of 72 kDa type IV collagenase (MMP2). [93]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A increases the expression of 72 kDa type IV collagenase (MMP2). [94]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate increases the activity of 72 kDa type IV collagenase (MMP2). [95]
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⏷ Show the Full List of 92 Drug(s)
5 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 72 kDa type IV collagenase (MMP2). [23]
Aspirin DM672AH Approved Aspirin decreases the secretion of 72 kDa type IV collagenase (MMP2). [28]
Glutathione DMAHMT9 Approved Glutathione decreases the secretion of 72 kDa type IV collagenase (MMP2). [40]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the secretion of 72 kDa type IV collagenase (MMP2). [55]
Arecoline DMFJZK3 Phase 1 Arecoline decreases the secretion of 72 kDa type IV collagenase (MMP2). [76]
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References

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