Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB2QDAV)

• DOT Name: Matrix metalloproteinase-9 (MMP9)
• Synonyms: MMP-9; EC 3.4.24.35; 92 kDa gelatinase; 92 kDa type IV collagenase; Gelatinase B; GELB
• Gene Name: MMP9
• Related Disease:
  Metaphyseal anadysplasia
  Metaphyseal anadysplasia 2
• UniProt ID: MMP9_HUMAN
• PDB ID: 1GKC; 1GKD; 1ITV; 1L6J; 2OVX; 2OVZ; 2OW0; 2OW1; 2OW2; 4H1Q; 4H2E; 4H3X; 4H82; 4HMA; 4JIJ; 4JQG; 4WZV; 4XCT; 5CUH; 5I12; 5TH6; 5TH9; 5UE3; 5UE4; 6ESM; 8K5V; 8K5W; 8K5X; 8K5Y
• EC Number: 3.4.24.35
• Pfam ID: PF00040 ; PF00045 ; PF00413
• Sequence:
  MSLWQPLVLVLLVLGCCFAAPRQRQSTLVLFPGDLRTNLTDRQLAEEYLYRYGYTRVAEM
  RGESKSLGPALLLLQKQLSLPETGELDSATLKAMRTPRCGVPDLGRFQTFEGDLKWHHHN
  ITYWIQNYSEDLPRAVIDDAFARAFALWSAVTPLTFTRVYSRDADIVIQFGVAEHGDGYP
  FDGKDGLLAHAFPPGPGIQGDAHFDDDELWSLGKGVVVPTRFGNADGAACHFPFIFEGRS
  YSACTTDGRSDGLPWCSTTANYDTDDRFGFCPSERLYTQDGNADGKPCQFPFIFQGQSYS
  ACTTDGRSDGYRWCATTANYDRDKLFGFCPTRADSTVMGGNSAGELCVFPFTFLGKEYST
  CTSEGRGDGRLWCATTSNFDSDKKWGFCPDQGYSLFLVAAHEFGHALGLDHSSVPEALMY
  PMYRFTEGPPLHKDDVNGIRHLYGPRPEPEPRPPTTTTPQPTAPPTVCPTGPPTVHPSER
  PTAGPTGPPSAGPTGPPTAGPSTATTVPLSPVDDACNVNIFDAIAEIGNQLYLFKDGKYW
  RFSEGRGSRPQGPFLIADKWPALPRKLDSVFEERLSKKLFFFSGRQVWVYTGASVLGPRR
  LDKLGLGADVAQVTGALRSGRGKMLLFSGRRLWRFDVKAQMVDPRSASEVDRMFPGVPLD
  THDVFQYREKAYFCQDRFYWRVSSRSELNQVDQVGYVTYDILQCPED
• Function: Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves NINJ1 to generate the Secreted ninjurin-1 form. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.
• Tissue Specificity: Detected in neutrophils (at protein level) . Produced by normal alveolar macrophages and granulocytes.
• KEGG Pathway:
  Endocrine resistance (hsa01522)
  IL-17 sig.ling pathway (hsa04657)
  TNF sig.ling pathway (hsa04668)
  Leukocyte transendothelial migration (hsa04670)
  Estrogen sig.ling pathway (hsa04915)
  Relaxin sig.ling pathway (hsa04926)
  Hepatitis B (hsa05161)
  Pathways in cancer (hsa05200)
  Transcriptio.l misregulation in cancer (hsa05202)
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)
  Prostate cancer (hsa05215)
  Bladder cancer (hsa05219)
  Diabetic cardiomyopathy (hsa05415)
  Lipid and atherosclerosis (hsa05417)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Collagen degradation (R-HSA-1442490)
  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)
  EPH-ephrin mediated repulsion of cells (R-HSA-3928665)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Neutrophil degranulation (R-HSA-6798695)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  Signaling by SCF-KIT (R-HSA-1433557)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Metaphyseal anadysplasia	DISQCPVO	Supportive	Autosomal dominant	[1]
Metaphyseal anadysplasia 2	DISNCNZ8	Limited	Unknown	[1]

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 Matrix metalloproteinase-9 (MMP9).	[2]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the methylation of Matrix metalloproteinase-9 (MMP9).	[83]

94 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 Matrix metalloproteinase-9 (MMP9).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Matrix metalloproteinase-9 (MMP9).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Matrix metalloproteinase-9 (MMP9).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Matrix metalloproteinase-9 (MMP9).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Matrix metalloproteinase-9 (MMP9).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Matrix metalloproteinase-9 (MMP9).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Matrix metalloproteinase-9 (MMP9).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Matrix metalloproteinase-9 (MMP9).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Matrix metalloproteinase-9 (MMP9).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Matrix metalloproteinase-9 (MMP9).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Matrix metalloproteinase-9 (MMP9).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Matrix metalloproteinase-9 (MMP9).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Matrix metalloproteinase-9 (MMP9).	[15]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Matrix metalloproteinase-9 (MMP9).	[16]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Matrix metalloproteinase-9 (MMP9).	[17]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Matrix metalloproteinase-9 (MMP9).	[18]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Matrix metalloproteinase-9 (MMP9).	[19]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Matrix metalloproteinase-9 (MMP9).	[20]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Matrix metalloproteinase-9 (MMP9).	[21]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Matrix metalloproteinase-9 (MMP9).	[22]
Menadione	DMSJDTY	Approved	Menadione decreases the expression of Matrix metalloproteinase-9 (MMP9).	[23]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Matrix metalloproteinase-9 (MMP9).	[24]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Matrix metalloproteinase-9 (MMP9).	[25]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Matrix metalloproteinase-9 (MMP9).	[26]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Matrix metalloproteinase-9 (MMP9).	[28]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Matrix metalloproteinase-9 (MMP9).	[29]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Matrix metalloproteinase-9 (MMP9).	[30]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the activity of Matrix metalloproteinase-9 (MMP9).	[31]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Matrix metalloproteinase-9 (MMP9).	[32]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Matrix metalloproteinase-9 (MMP9).	[33]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Matrix metalloproteinase-9 (MMP9).	[34]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Matrix metalloproteinase-9 (MMP9).	[35]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Matrix metalloproteinase-9 (MMP9).	[36]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Matrix metalloproteinase-9 (MMP9).	[37]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the activity of Matrix metalloproteinase-9 (MMP9).	[38]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Matrix metalloproteinase-9 (MMP9).	[39]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Matrix metalloproteinase-9 (MMP9).	[40]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Matrix metalloproteinase-9 (MMP9).	[41]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Matrix metalloproteinase-9 (MMP9).	[42]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Matrix metalloproteinase-9 (MMP9).	[43]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Matrix metalloproteinase-9 (MMP9).	[44]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Matrix metalloproteinase-9 (MMP9).	[45]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the expression of Matrix metalloproteinase-9 (MMP9).	[46]
Dinoprostone	DMTYOPD	Approved	Dinoprostone increases the expression of Matrix metalloproteinase-9 (MMP9).	[47]
Dactinomycin	DM2YGNW	Approved	Dactinomycin decreases the expression of Matrix metalloproteinase-9 (MMP9).	[48]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Matrix metalloproteinase-9 (MMP9).	[49]
Lovastatin	DM9OZWQ	Approved	Lovastatin decreases the expression of Matrix metalloproteinase-9 (MMP9).	[50]
Ardeparin	DMYRX8B	Approved	Ardeparin decreases the activity of Matrix metalloproteinase-9 (MMP9).	[51]
Melatonin	DMKWFBT	Approved	Melatonin decreases the expression of Matrix metalloproteinase-9 (MMP9).	[52]
Artesunate	DMR27C8	Approved	Artesunate decreases the expression of Matrix metalloproteinase-9 (MMP9).	[53]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the expression of Matrix metalloproteinase-9 (MMP9).	[54]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Approved	Eicosapentaenoic acid/docosa-hexaenoic acid decreases the expression of Matrix metalloproteinase-9 (MMP9).	[56]
Ximelegatran	DMU8ANS	Approved	Ximelegatran decreases the expression of Matrix metalloproteinase-9 (MMP9).	[57]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose decreases the expression of Matrix metalloproteinase-9 (MMP9).	[58]
Cantharidin	DMBP5N3	Approved	Cantharidin decreases the expression of Matrix metalloproteinase-9 (MMP9).	[59]
Fructose	DM43AN2	Approved	Fructose increases the expression of Matrix metalloproteinase-9 (MMP9).	[60]
Propranolol	DM79NTF	Approved	Propranolol decreases the expression of Matrix metalloproteinase-9 (MMP9).	[62]
Phenylephrine	DMZHUO5	Approved	Phenylephrine increases the expression of Matrix metalloproteinase-9 (MMP9).	[49]
Flurbiprofen	DMGN4BY	Approved	Flurbiprofen decreases the expression of Matrix metalloproteinase-9 (MMP9).	[63]
Nicotinamide	DMUPE07	Approved	Nicotinamide increases the expression of Matrix metalloproteinase-9 (MMP9).	[64]
Carvedilol	DMHTEAO	Approved	Carvedilol affects the activity of Matrix metalloproteinase-9 (MMP9).	[49]
Norepinephrine	DMOUC09	Approved	Norepinephrine increases the expression of Matrix metalloproteinase-9 (MMP9).	[65]
Sanguinarine	DMDINFS	Approved	Sanguinarine decreases the expression of Matrix metalloproteinase-9 (MMP9).	[66]
Abacavir	DMMN36E	Approved	Abacavir increases the expression of Matrix metalloproteinase-9 (MMP9).	[67]
Fludarabine	DMVRLT7	Approved	Fludarabine increases the expression of Matrix metalloproteinase-9 (MMP9).	[48]
Terbinafine	DMI6HUW	Approved	Terbinafine decreases the expression of Matrix metalloproteinase-9 (MMP9).	[68]
Emetine	DMCT2YF	Approved	Emetine decreases the expression of Matrix metalloproteinase-9 (MMP9).	[69]
Metoprolol	DMOJ0V6	Approved	Metoprolol decreases the expression of Matrix metalloproteinase-9 (MMP9).	[62]
Benazepril	DMH1M9B	Approved	Benazepril decreases the expression of Matrix metalloproteinase-9 (MMP9).	[70]
Regorafenib	DMHSY1I	Approved	Regorafenib decreases the expression of Matrix metalloproteinase-9 (MMP9).	[71]
Tetracaine	DM9J6C2	Approved	Tetracaine decreases the expression of Matrix metalloproteinase-9 (MMP9).	[72]
Idelalisib	DM602WT	Approved	Idelalisib decreases the expression of Matrix metalloproteinase-9 (MMP9).	[74]
Cysteamine	DMSYFM8	Approved	Cysteamine increases the expression of Matrix metalloproteinase-9 (MMP9).	[75]
Pentosan polysulfate	DM2HRKE	Approved	Pentosan polysulfate increases the expression of Matrix metalloproteinase-9 (MMP9).	[76]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the activity of Matrix metalloproteinase-9 (MMP9).	[77]
Beclomethasone dipropionate	DM5NW1E	Phase 4	Beclomethasone dipropionate decreases the expression of Matrix metalloproteinase-9 (MMP9).	[78]
Glyceryl trinitrate	DMF72W3	Phase 4	Glyceryl trinitrate increases the expression of Matrix metalloproteinase-9 (MMP9).	[79]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Matrix metalloproteinase-9 (MMP9).	[80]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Matrix metalloproteinase-9 (MMP9).	[81]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the activity of Matrix metalloproteinase-9 (MMP9).	[82]
Rigosertib	DMOSTXF	Phase 3	Rigosertib affects the expression of Matrix metalloproteinase-9 (MMP9).	[84]
HMPL-004	DM29XGY	Phase 3	HMPL-004 decreases the expression of Matrix metalloproteinase-9 (MMP9).	[85]
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine decreases the expression of Matrix metalloproteinase-9 (MMP9).	[86]
ICI 118,551	DM3OU54	Phase 3	ICI 118,551 decreases the expression of Matrix metalloproteinase-9 (MMP9).	[62]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Matrix metalloproteinase-9 (MMP9).	[87]
Thymoquinone	DMVDTR2	Phase 2/3	Thymoquinone decreases the expression of Matrix metalloproteinase-9 (MMP9).	[88]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Matrix metalloproteinase-9 (MMP9).	[89]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram decreases the expression of Matrix metalloproteinase-9 (MMP9).	[90]
BAICALEIN	DM4C7E6	Phase 2	BAICALEIN decreases the activity of Matrix metalloproteinase-9 (MMP9).	[91]
URSOLIC ACID	DM4SOAW	Phase 2	URSOLIC ACID decreases the expression of Matrix metalloproteinase-9 (MMP9).	[92]
G1	DMTV42K	Phase 1/2	G1 increases the activity of Matrix metalloproteinase-9 (MMP9).	[93]
Taurocholic acid	DM2LZ8F	Phase 1/2	Taurocholic acid increases the expression of Matrix metalloproteinase-9 (MMP9).	[94]
PIPERINE	DMYEAB1	Phase 1/2	PIPERINE decreases the expression of Matrix metalloproteinase-9 (MMP9).	[95]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Matrix metalloproteinase-9 (MMP9).	[96]

4 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 Matrix metalloproteinase-9 (MMP9).	[27]
Glutathione	DMAHMT9	Approved	Glutathione decreases the secretion of Matrix metalloproteinase-9 (MMP9).	[55]
Clofibrate	DMPC1J7	Approved	Clofibrate decreases the secretion of Matrix metalloproteinase-9 (MMP9).	[61]
Hesperidin	DMI5DW1	Approved	Hesperidin decreases the secretion of Matrix metalloproteinase-9 (MMP9).	[73]

References

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