Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Matrix metalloproteinase-7 (MMP-7)
• Synonyms: Uterine metalloproteinase; Pump-1 protease; PUMP1; Matrin; Matrilysin; MPSL1
• Gene Name: MMP7
• DTT Type: Successful target; [1]
• BioChemical Class: Peptidase
• UniProt ID: MMP7_HUMAN
• TTD ID: T73475
• EC Number: EC 3.4.24.23
• Sequence:
  MRLTVLCAVCLLPGSLALPLPQEAGGMSELQWEQAQDYLKRFYLYDSETKNANSLEAKLK
  EMQKFFGLPITGMLNSRVIEIMQKPRCGVPDVAEYSLFPNSPKWTSKVVTYRIVSYTRDL
  PHITVDRLVSKALNMWGKEIPLHFRKVVWGTADIMIGFARGAHGDSYPFDGPGNTLAHAF
  APGTGLGGDAHFDEDERWTDGSSLGINFLYAATHELGHSLGMGHSSDPNAVMYPTYGNGD
  PQNFKLSQDDIKGIQKLYGKRSNSRKK
• Function: Activates procollagenase. Degrades casein, gelatins of types I, III, IV, and V, and fibronectin.
• KEGG Pathway: Wnt signaling pathway (hsa04310)
• 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)
  Collagen degradation (R-HSA-1442490)

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]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Marimastat	DM6V34C	Pancreatic cancer	2C10	Phase 3	[2]

3 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	[3]
BB-3644	DM7YRFE	Solid tumour/cancer	2A00-2F9Z	Terminated	[4]
SC-44463	DMBPNKT	N. A.	N. A.	Terminated	[5]

11 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3-Benzenesulfonyl-heptanoic acid hydroxyamide	DM7XDCF	Discovery agent	N.A.	Investigative	[6]
3-Cyclohexanesulfonyl-heptanoic acid hydroxyamide	DMJSOTE	Discovery agent	N.A.	Investigative	[6]
Folate gamma-hydroxamic acid	DMJ4F3Q	Discovery agent	N.A.	Investigative	[7]
Folate gamma-L-phenylalaninehydroxamic acid	DM76AUO	Discovery agent	N.A.	Investigative	[7]
Folate gamma-L-proline-hydroxamic acid	DMH5SQV	Discovery agent	N.A.	Investigative	[7]
IK-862	DMJA4UE	Discovery agent	N.A.	Investigative	[8]
MMI270	DM38N2K	Discovery agent	N.A.	Investigative	[7]
N-hydroxy-2,3-bis(phenylsulfonamido)propanamide	DMZWIVJ	Discovery agent	N.A.	Investigative	[9]
RS-39066	DM2SCM7	Discovery agent	N.A.	Investigative	[10]
SL422	DM3I2US	Discovery agent	N.A.	Investigative	[11]
SR-973	DMU48OD	Discovery agent	N.A.	Investigative	[12]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Sarcoma	2C82	Muscle tissue	4.87E-01	-0.2	-0.57
Prostate cancer	2C82	Prostate	4.44E-01	-0.19	-0.09
Lung cancer	2C82	Lung tissue	6.83E-17	0.96	0.8

References

• [1] AG-3340 (Agouron Pharmaceuticals Inc). IDrugs. 2000 Mar;3(3):336-45.
• [2] Metalloelastase (MMP-12) induced inflammatory response in mice airways: effects of dexamethasone, rolipram and marimastat. Eur J Pharmacol. 2007 Mar 15;559(1):75-81.
• [3] Phase 1/2 trial of BMS-275291 in patients with human immunodeficiency virus-related Kaposi sarcoma: a multicenter trial of the AIDS Malignancy Consortium. Cancer. 2008 Mar 1;112(5):1083-8.
• [4] Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat Rev Cancer. 2006 Mar;6(3):227-39.
• [5] A potent, selective inhibitor of matrix metalloproteinase-3 for the topical treatment of chronic dermal ulcers. J Med Chem. 2003 Jul 31;46(16):3514-25.
• [6] Hydroxamic acid derivatives as potent peptide deformylase inhibitors and antibacterial agents. J Med Chem. 2000 Jun 15;43(12):2324-31.
• [7] Methotrexate gamma-hydroxamate derivatives as potential dual target antitumor drugs. Bioorg Med Chem. 2007 Feb 1;15(3):1266-74.
• [8] Discovery of gamma-lactam hydroxamic acids as selective inhibitors of tumor necrosis factor alpha converting enzyme: design, synthesis, and structu... J Med Chem. 2002 Nov 7;45(23):4954-7.
• [9] Novel bis-(arylsulfonamide) hydroxamate-based selective MMP inhibitors. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3333-7.
• [10] Design, synthesis, activity, and structure of a novel class of matrix metalloproteinase inhibitors containing a heterocyclic P2 P3 Bioorg. Med. Chem. Lett. 6(13):1541-1542 (1996).
• [11] Design, synthesis, and structure-activity relationships of macrocyclic hydroxamic acids that inhibit tumor necrosis factor alpha release in vitro and in vivo. J Med Chem. 2001 Aug 2;44(16):2636-60.
• [12] Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors. Bioorg Med Chem Lett. 2006 May 1;16(9):2357-63.