Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTLM12X)

• DTT Name: Matrix metalloproteinase-2 (MMP-2)
• Synonyms: TBE-1; Matrix metalloproteinase 2; CLG4A; 72 kDa type IV collagenase; 72 kDa gelatinase
• Gene Name: MMP2
• DTT Type: Successful target; [1]
• BioChemical Class: Peptidase
• UniProt ID: MMP2_HUMAN
• TTD ID: T68251
• EC Number: EC 3.4.24.24
• Sequence:
  MEALMARGALTGPLRALCLLGCLLSHAAAAPSPIIKFPGDVAPKTDKELAVQYLNTFYGC
  PKESCNLFVLKDTLKKMQKFFGLPQTGDLDQNTIETMRKPRCGNPDVANYNFFPRKPKWD
  KNQITYRIIGYTPDLDPETVDDAFARAFQVWSDVTPLRFSRIHDGEADIMINFGRWEHGD
  GYPFDGKDGLLAHAFAPGTGVGGDSHFDDDELWTLGEGQVVRVKYGNADGEYCKFPFLFN
  GKEYNSCTDTGRSDGFLWCSTTYNFEKDGKYGFCPHEALFTMGGNAEGQPCKFPFRFQGT
  SYDSCTTEGRTDGYRWCGTTEDYDRDKKYGFCPETAMSTVGGNSEGAPCVFPFTFLGNKY
  ESCTSAGRSDGKMWCATTANYDDDRKWGFCPDQGYSLFLVAAHEFGHAMGLEHSQDPGAL
  MAPIYTYTKNFRLSQDDIKGIQELYGASPDIDLGTGPTPTLGPVTPEICKQDIVFDGIAQ
  IRGEIFFFKDRFIWRTVTPRDKPMGPLLVATFWPELPEKIDAVYEAPQEEKAVFFAGNEY
  WIYSASTLERGYPKPLTSLGLPPDVQRVDAAFNWSKNKKTYIFAGDKFWRYNEVKKKMDP
  GFPKLIADAWNAIPDNLDAVVDLQGGGHSYFFKGAYYLKLENQSLKSVKFGSIKSDWLGC
• Function: 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. Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture.
• KEGG Pathway:
  Leukocyte transendothelial migration (hsa04670)
  GnRH signaling pathway (hsa04912)
  Estrogen signaling pathway (hsa04915)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Bladder cancer (hsa05219)
• 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)
  Collagen degradation (R-HSA-1442490)
• BioCyc Pathway: MetaCyc:HS01565-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Prinomastat	DM9HOKG	Lung cancer	2C25.0	Approved	[1]

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Epigallocatechin gallate	DMCGWBJ	Hepatic fibrosis	DB93.0	Phase 3	[2]
Marimastat	DM6V34C	Pancreatic cancer	2C10	Phase 3	[3]
Metastat	DMTQ4PN	Acne vulgaris	ED80	Phase 1	[4]
Neovastat	DMXTYWJ	Non-small-cell lung cancer	2C25.Y	Phase 1	[5]

10 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID29130358-Compound-Figure10(2a)	DMFWXPS	N. A.	N. A.	Patented	[6]
PMID29130358-Compound-Figure11(3)	DMSME2B	N. A.	N. A.	Patented	[6]
PMID29130358-Compound-Figure13(4)	DMDFPIO	N. A.	N. A.	Patented	[6]
PMID29130358-Compound-Figure16(9a)	DMKX5R8	N. A.	N. A.	Patented	[6]
PMID29130358-Compound-Figure16(9b)	DMPAQLZ	N. A.	N. A.	Patented	[6]
PMID29130358-Compound-Figure16(9c)	DM0ZRI9	N. A.	N. A.	Patented	[6]
PMID29130358-Compound-Figure18(14)	DM7WXJ9	N. A.	N. A.	Patented	[6]
PMID29130358-Compound-Figure18(14a)	DMHIBTZ	N. A.	N. A.	Patented	[6]
PMID29130358-Compound-LonimacranthoideVII	DMOGIAU	N. A.	N. A.	Patented	[6]
PMID29130358-Compound-SB-3CT	DMC64XQ	N. A.	N. A.	Patented	[6]

10 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BMS 275291	DMKSFPE	Kaposi sarcoma	2B57	Discontinued in Phase 3	[7]
Tanomastat	DMVB9XC	Lung cancer	2C25.0	Discontinued in Phase 3	[8]
Galarubicin	DMTNYSF	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[9]
GM6001	DM7V9CT	Corneal ulcer	9A76	Discontinued in Phase 2	[10]
RS-130830	DMOTANY	Hepatitis C virus infection	1E51.1	Discontinued in Phase 2	[11]
BB-1101	DM7GH5Z	Multiple sclerosis	8A40	Terminated	[13]
BB-3644	DM7YRFE	Solid tumour/cancer	2A00-2F9Z	Terminated	[14]
CDP-845	DMGMS2D	Solid tumour/cancer	2A00-2F9Z	Terminated	[15]
L-696418	DMV785R	N. A.	N. A.	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
RO-26-2853	DM3ZE5A	Solid tumour/cancer	2A00-2F9Z	Preclinical	[12]

30 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-ylsulfonyl)N-hydroxybenzamide	DMCNV5J	Discovery agent	N.A.	Investigative	[20]
3-(4-(2-phenylethynyl)benzoyl)pentanoic acid	DMQDPHT	Discovery agent	N.A.	Investigative	[21]
3-(4-Phenylethynylbenzoyl)nonanoic acid	DMXL0J5	Discovery agent	N.A.	Investigative	[21]
4-(4-(dec-1-ynyl)phenyl)-4-oxobutanoic acid	DM6KIG0	Discovery agent	N.A.	Investigative	[21]
5-(4-Phenoxy-phenyl)-pyrimidine-2,4,6-trione	DM05OMF	Discovery agent	N.A.	Investigative	[22]
5-Biphenyl-4-yl-5-ethyl-pyrimidine-2,4,6-trione	DMFAITE	Discovery agent	N.A.	Investigative	[22]
5-Biphenyl-4-yl-5-hexyl-pyrimidine-2,4,6-trione	DMI2PXO	Discovery agent	N.A.	Investigative	[22]
5-Hexyl-5-phenyl-pyrimidine-2,4,6-trione	DM4S86L	Discovery agent	N.A.	Investigative	[22]
Cis-2-aminocyclohexylcarbamoylphosphonic acid	DMF10WT	Discovery agent	N.A.	Investigative	[23]
Clinopodic acid C	DMS58P1	Discovery agent	N.A.	Investigative	[24]
Folate gamma-hydroxamic acid	DMJ4F3Q	Discovery agent	N.A.	Investigative	[25]
Folate gamma-L-proline-hydroxamic acid	DMH5SQV	Discovery agent	N.A.	Investigative	[25]
IK-862	DMJA4UE	Discovery agent	N.A.	Investigative	[26]
Lithospermic acid	DMPAKQV	Discovery agent	N.A.	Investigative	[24]
Methotrexate gamma-hydroxamic acid	DM8P526	Discovery agent	N.A.	Investigative	[25]
Methotrexate gamma-L-proline-hydroxamic acid	DMPYJLA	Discovery agent	N.A.	Investigative	[25]
MMI270	DM38N2K	Discovery agent	N.A.	Investigative	[27]
N-Hydroxy-2-(4-phenoxy-benzenesulfonyl)benzamide	DM4VADN	Discovery agent	N.A.	Investigative	[20]
N-hydroxy-3-(2-oxo-2H-chromen-3-yl)propanamide	DMWXUCT	Discovery agent	N.A.	Investigative	[28]
N-hydroxy-3-(6-methoxy-2-oxo-2H-chromen-3-yl)	DMA6EPH	Discovery agent	N.A.	Investigative	[28]
PD-169469	DMU3OR1	Discovery agent	N.A.	Investigative	[29]
PNU-107859	DMS5XRY	Discovery agent	N.A.	Investigative	[30]
Ro-37-9790	DM83QMZ	Discovery agent	N.A.	Investigative	[31]
Roche 28-2653	DMD4JHK	Discovery agent	N.A.	Investigative	[32]
SC-74020	DMNI91Z	Discovery agent	N.A.	Investigative	[33]
SR-973	DMU48OD	Discovery agent	N.A.	Investigative	[34]
UK-356618	DM02FGH	Discovery agent	N.A.	Investigative	[17]
[2-(Biphenyl-4-sulfonyl)phenyl]acetic Acid	DM37C25	Discovery agent	N.A.	Investigative	[20]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Sarcoma	2C82	Muscle tissue	3.48E-16	-0.11	-0.43
Renal cancer	2C82	Kidney	1.23E-01	-0.29	-1.11
Ovarian cancer	2C82	Ovarian tissue	8.96E-02	-0.22	-0.61
Osteoarthritis	FA20	Synovial tissue	4.90E-01	-0.07	-0.5
Prostate cancer	2C82	Prostate	3.15E-02	-0.29	-0.56
Lung cancer	2C82	Lung tissue	8.17E-01	0.03	0.1
Rheumatoid arthritis	FA20	Synovial tissue	1.29E-01	0.25	0.83

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