Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT6X50U)

• DTT Name: Matrix metalloproteinase-9 (MMP-9)
• Synonyms: Matrix metalloproteinase 9; GELB; CLG4B; 92 kDa type IV collagenase; 92 kDa gelatinase
• Gene Name: MMP9
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Ischaemic/haemorrhagic stroke [ICD-11: 8B20]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]
  Stomach cancer [ICD-11: 2B72]
  Ulcerative colitis [ICD-11: DD71]
• BioChemical Class: Peptidase
• UniProt ID: MMP9_HUMAN
• TTD ID: T54156
• EC Number: EC 3.4.24.35
• Sequence:
  MSLWQPLVLVLLVLGCCFAAPRQRQSTLVLFPGDLRTNLTDRQLAEEYLYRYGYTRVAEM
  RGESKSLGPALLLLQKQLSLPETGELDSATLKAMRTPRCGVPDLGRFQTFEGDLKWHHHN
  ITYWIQNYSEDLPRAVIDDAFARAFALWSAVTPLTFTRVYSRDADIVIQFGVAEHGDGYP
  FDGKDGLLAHAFPPGPGIQGDAHFDDDELWSLGKGVVVPTRFGNADGAACHFPFIFEGRS
  YSACTTDGRSDGLPWCSTTANYDTDDRFGFCPSERLYTQDGNADGKPCQFPFIFQGQSYS
  ACTTDGRSDGYRWCATTANYDRDKLFGFCPTRADSTVMGGNSAGELCVFPFTFLGKEYST
  CTSEGRGDGRLWCATTSNFDSDKKWGFCPDQGYSLFLVAAHEFGHALGLDHSSVPEALMY
  PMYRFTEGPPLHKDDVNGIRHLYGPRPEPEPRPPTTTTPQPTAPPTVCPTGPPTVHPSER
  PTAGPTGPPSAGPTGPPTAGPSTATTVPLSPVDDACNVNIFDAIAEIGNQLYLFKDGKYW
  RFSEGRGSRPQGPFLIADKWPALPRKLDSVFEERLSKKLFFFSGRQVWVYTGASVLGPRR
  LDKLGLGADVAQVTGALRSGRGKMLLFSGRRLWRFDVKAQMVDPRSASEVDRMFPGVPLD
  THDVFQYREKAYFCQDRFYWRVSSRSELNQVDQVGYVTYDILQCPED
• Function: Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. 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. May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration.
• KEGG Pathway:
  TNF signaling pathway (hsa04668)
  Leukocyte transendothelial migration (hsa04670)
  Estrogen signaling pathway (hsa04915)
  Hepatitis B (hsa05161)
  Pathways in cancer (hsa05200)
  Transcriptional misregulation in cancer (hsa05202)
  Proteoglycans in cancer (hsa05205)
  MicroRNAs in cancer (hsa05206)
  Bladder cancer (hsa05219)
• 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)
  EPH-ephrin mediated repulsion of cells (R-HSA-3928665)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DTT

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Andecaliximab	DMLDB1X	Gastric adenocarcinoma	2B72	Phase 3	[2]
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[1]
DP-b99	DM97S10	Stroke	8B20	Phase 3	[3]
GS-5745	DMP8MDW	Gastric adenocarcinoma	2B72	Phase 3	[4]
BLZ-100	DMFKA4G	Glioma	2A00.0	Phase 1/2	[5]
Neovastat	DMXTYWJ	Non-small-cell lung cancer	2C25.Y	Phase 1	[6], [7], [8]

8 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID29130358-Compound-Figure13(4)	DMDFPIO	N. A.	N. A.	Patented	[9]
PMID29130358-Compound-Figure17(10)	DMVA15O	N. A.	N. A.	Patented	[9]
PMID29130358-Compound-Figure17(11)	DMSZA9L	N. A.	N. A.	Patented	[9]
PMID29130358-Compound-Figure17(12)	DMML4PA	N. A.	N. A.	Patented	[9]
PMID29130358-Compound-Figure17(13)	DM2QRIW	N. A.	N. A.	Patented	[9]
PMID29130358-Compound-Figure18(14a)	DMHIBTZ	N. A.	N. A.	Patented	[9]
PMID29130358-Compound-LonimacranthoideVII	DMOGIAU	N. A.	N. A.	Patented	[9]
PMID29130358-Compound-SB-3CT	DMC64XQ	N. A.	N. A.	Patented	[9]

7 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Galarubicin	DMTNYSF	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[10]
GM6001	DM7V9CT	Corneal ulcer	9A76	Discontinued in Phase 2	[11]
RS-130830	DMOTANY	Hepatitis C virus infection	1E51.1	Discontinued in Phase 2	[12]
CDP-845	DMGMS2D	Solid tumour/cancer	2A00-2F9Z	Terminated	[14]
CT-1746	DM84KOY	Colorectal cancer	2B91.Z	Terminated	[15]
RO-319790	DML3NEU	Rheumatoid arthritis	FA20	Terminated	[16]
SC-44463	DMBPNKT	N. A.	N. A.	Terminated	[17]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DX-2802	DM8YSW7	Solid tumour/cancer	2A00-2F9Z	Preclinical	[13]

34 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+/-)5-(biphenyl-4-yl)-3-hydroxypentanoic acid	DMSN7GJ	Discovery agent	N.A.	Investigative	[18]
2-(4'-chloro-biphenyl-4-sulfonyl)-pentanoic acid	DMQAVM4	Discovery agent	N.A.	Investigative	[19]
2-(biphenyl-4-ylsulfonamido)pentanedioic acid	DMH3YBR	Discovery agent	N.A.	Investigative	[20]
2-(Biphenyl-4-ylsulfonyl)N-hydroxybenzamide	DMCNV5J	Discovery agent	N.A.	Investigative	[21]
2-Amino-N,3,3-Trimethylbutanamide	DM3YI9P	Discovery agent	N.A.	Investigative	[22]
3-(4-(2-phenylethynyl)benzoyl)pentanoic acid	DMQDPHT	Discovery agent	N.A.	Investigative	[23]
3-(4-Phenylethynylbenzoyl)nonanoic acid	DMXL0J5	Discovery agent	N.A.	Investigative	[23]
4-amino-3-(4-(hexyloxy)phenyl)-4-oxobutanoic acid	DMGI0YV	Discovery agent	N.A.	Investigative	[20]
5-(4-Phenoxy-phenyl)-pyrimidine-2,4,6-trione	DM05OMF	Discovery agent	N.A.	Investigative	[24]
5-Biphenyl-4-yl-5-ethyl-pyrimidine-2,4,6-trione	DMFAITE	Discovery agent	N.A.	Investigative	[24]
5-Biphenyl-4-yl-5-hexyl-pyrimidine-2,4,6-trione	DMI2PXO	Discovery agent	N.A.	Investigative	[24]
5-Hexyl-5-phenyl-pyrimidine-2,4,6-trione	DM4S86L	Discovery agent	N.A.	Investigative	[24]
5-Methyl-5-phenyl-pyrimidine-2,4,6-trione	DMRMKXD	Discovery agent	N.A.	Investigative	[24]
ARP100	DM6KQXF	Discovery agent	N.A.	Investigative	[25]
Carboxylated glucosamine	DM105YR	Discovery agent	N.A.	Investigative	[26]
Folate gamma-hydroxamic acid	DMJ4F3Q	Discovery agent	N.A.	Investigative	[27]
IK-862	DMJA4UE	Discovery agent	N.A.	Investigative	[28]
Methotrexate gamma-hydroxamic acid	DM8P526	Discovery agent	N.A.	Investigative	[27]
Methotrexate gamma-L-phenylalaninehydroxamic acid	DMELK2A	Discovery agent	N.A.	Investigative	[27]
Methotrexate gamma-L-proline-hydroxamic acid	DMPYJLA	Discovery agent	N.A.	Investigative	[27]
MMI270	DM38N2K	Discovery agent	N.A.	Investigative	[29]
N-hydroxy-2,3-bis(phenylsulfonamido)propanamide	DMZWIVJ	Discovery agent	N.A.	Investigative	[30]
N-Hydroxy-2-(4-phenoxy-benzenesulfonyl)benzamide	DM4VADN	Discovery agent	N.A.	Investigative	[21]
N-hydroxy-3-(2-oxo-2H-chromen-3-yl)propanamide	DMWXUCT	Discovery agent	N.A.	Investigative	[31]
N-hydroxy-3-(6-methoxy-2-oxo-2H-chromen-3-yl)	DMA6EPH	Discovery agent	N.A.	Investigative	[31]
PMID15055993C1a	DM9V6YK	Discovery agent	N.A.	Investigative	[32]
PMID23631440C29e	DMM92IB	Discovery agent	N.A.	Investigative	[33]
Ro 28-2653	DMDC4HY	Discovery agent	N.A.	Investigative	[34]
Ro-37-9790	DM83QMZ	Discovery agent	N.A.	Investigative	[35]
Roche 28-2653	DMD4JHK	Discovery agent	N.A.	Investigative	[34]
SL422	DM3I2US	Discovery agent	N.A.	Investigative	[36]
SR-973	DMU48OD	Discovery agent	N.A.	Investigative	[37]
UK-356618	DM02FGH	Discovery agent	N.A.	Investigative	[38]
[2-(Biphenyl-4-sulfonyl)phenyl]acetic Acid	DM37C25	Discovery agent	N.A.	Investigative	[21]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Renal cancer	2C82	Kidney	1.12E-10	1.15	3.45
Lung cancer	2C82	Lung tissue	3.53E-54	2.03	1.94
Rheumatoid arthritis	FA20	Synovial tissue	7.66E-05	0.81	1.83
Ovarian cancer	2C82	Ovarian tissue	1.15E-07	1.57	3.98
Osteoarthritis	FA20	Synovial tissue	2.59E-01	0.11	0.25

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Matrix metalloproteinase-9 (MMP-9) DME Info
• Gene Name: MMP9

1 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amylin	DMWDEN0	N. A.	N. A.	Phase 4	[39]

References

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