Target Information

Target General Infomation
Target ID
T73475
Former ID
TTDR00029
Target Name
Matrilysin
Gene Name
MMP7
Synonyms
MMP-7; Matrin; Matrix metalloproteinase-7; Pump-1 protease; Uterine metalloproteinase; MMP7
Target Type
Successful
Disease Brain cancer [ICD9: 191, 225.0; ICD10: C71, D33]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Lung cancer; Prostate cancer [ICD9: 140-229, 162, 185; ICD10: C33-C34, C61]
Non-small-cell lung cancer; Hormone-refractory prostate cancer; Kaposi's sarcoma [ICD9: 140-229, 162, 176, 185, 204.0; ICD10: C33, C33-C34, C34, C46, C61, C91.0]
Pancreatic cancer; Lung cancer [ICD9: 140-229, 157, 162; ICD10: C25, C33-C34]
Pancreatic cancer [ICD9: 140-199, 140-229, 157, 210-229; ICD10: C25]
Function
Degrades casein, gelatins of types I, III, IV, and V, and fibronectin. Activates procollagenase.
BioChemical Class
Peptidase
Target Validation
T73475
UniProt ID
P09237
EC Number
EC 3.4.24.23
Sequence
MRLTVLCAVCLLPGSLALPLPQEAGGMSELQWEQAQDYLKRFYLYDSETKNANSLEAKLK
EMQKFFGLPITGMLNSRVIEIMQKPRCGVPDVAEYSLFPNSPKWTSKVVTYRIVSYTRDL
PHITVDRLVSKALNMWGKEIPLHFRKVVWGTADIMIGFARGAHGDSYPFDGPGNTLAHAF
APGTGLGGDAHFDEDERWTDGSSLGINFLYAATHELGHSLGMGHSSDPNAVMYPTYGNGD
PQNFKLSQDDIKGIQKLYGKRSNSRKK
Drugs and Mode of Action
Drug(s) Prinomastat Drug Info Approved Lung cancer; Prostate cancer [536056], [541642]
Marimastat Drug Info Phase 3 Pancreatic cancer [468274], [527314]
BMS 275291 Drug Info Discontinued in Phase 3 Non-small-cell lung cancer; Hormone-refractory prostate cancer; Kaposi's sarcoma [536608]
Marimastat Drug Info Discontinued in Phase 3 Pancreatic cancer; Lung cancer [468274], [536223]
Prinomastat Drug Info Discontinued in Phase 3 Brain cancer [536056], [541642]
BB-3644 Drug Info Terminated Cancer [535909]
SC-44463 Drug Info Terminated Discovery agent [546364]
Inhibitor 3-Benzenesulfonyl-heptanoic acid hydroxyamide Drug Info [525813]
3-Cyclohexanesulfonyl-heptanoic acid hydroxyamide Drug Info [525813]
BB-3644 Drug Info [528049], [535909]
BMS 275291 Drug Info [528049], [536019], [536073], [536608]
Folate gamma-hydroxamic acid Drug Info [528548]
Folate gamma-L-phenylalaninehydroxamic acid Drug Info [528548]
Folate gamma-L-proline-hydroxamic acid Drug Info [528548]
IK-682 Drug Info [526446]
Marimastat Drug Info [528049], [536340], [537040], [538064]
MMI270 Drug Info [528548]
N-hydroxy-2,3-bis(phenylsulfonamido)propanamide Drug Info [529443]
Prinomastat Drug Info [528049], [536127], [536723], [536808], [537136]
RS-39066 Drug Info [551301]
SC-44463 Drug Info [526680]
SL422 Drug Info [526113]
SR-973 Drug Info [528025]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Wnt signaling pathway
NetPath Pathway Wnt Signaling Pathway
PANTHER Pathway Alzheimer disease-presenilin pathway
Wnt signaling pathway
CCKR signaling map ST
Pathway Interaction Database Posttranslational regulation of adherens junction stability and dissassembly
p75(NTR)-mediated signaling
Syndecan-1-mediated signaling events
Reactome Collagen degradation
Degradation of the extracellular matrix
Activation of Matrix Metalloproteinases
Assembly of collagen fibrils and other multimeric structures
WikiPathways Wnt Signaling Pathway and Pluripotency
Activation of Matrix Metalloproteinases
AGE/RAGE pathway
Matrix Metalloproteinases
References
Ref 468274(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5220).
Ref 527314Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196. J Clin Oncol. 2004 Dec 1;22(23):4683-90.
Ref 535909A phase I and pharmacological study of the matrix metalloproteinase inhibitor BB-3644 in patients with solid tumours. Br J Cancer. 2004 Feb 23;90(4):800-4.
Ref 536056Emerging therapies for neuropathic pain. Expert Opin Emerg Drugs. 2005 Feb;10(1):95-108.
Ref 536223Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
Ref 536608Phase 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.
Ref 541642(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6505).
Ref 546364Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007717)
Ref 525813J Med Chem. 2000 Jun 15;43(12):2324-31.Hydroxamic acid derivatives as potent peptide deformylase inhibitors and antibacterial agents.
Ref 526113Design, 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.
Ref 526446J Med Chem. 2002 Nov 7;45(23):4954-7.Discovery of gamma-lactam hydroxamic acids as selective inhibitors of tumor necrosis factor alpha converting enzyme: design, synthesis, and structure-activity relationships.
Ref 526680J Med Chem. 2003 Jul 31;46(16):3514-25.A potent, selective inhibitor of matrix metalloproteinase-3 for the topical treatment of chronic dermal ulcers.
Ref 528025Bioorg Med Chem Lett. 2006 May 1;16(9):2357-63. Epub 2006 Feb 10.Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors.
Ref 528049Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat Rev Cancer. 2006 Mar;6(3):227-39.
Ref 528548Bioorg Med Chem. 2007 Feb 1;15(3):1266-74. Epub 2006 Nov 14.Methotrexate gamma-hydroxamate derivatives as potential dual target antitumor drugs.
Ref 529443Bioorg Med Chem Lett. 2008 Jun 1;18(11):3333-7. Epub 2008 Apr 16.Novel bis-(arylsulfonamide) hydroxamate-based selective MMP inhibitors.
Ref 535909A phase I and pharmacological study of the matrix metalloproteinase inhibitor BB-3644 in patients with solid tumours. Br J Cancer. 2004 Feb 23;90(4):800-4.
Ref 536019Randomized phase II feasibility study of combining the matrix metalloproteinase inhibitor BMS-275291 with paclitaxel plus carboplatin in advanced non-small cell lung cancer. Lung Cancer. 2004 Dec;46(3):361-8.
Ref 536073Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR.18. J Clin Oncol. 2005 Apr 20;23(12):2831-9.
Ref 536127AG-3340 (Agouron Pharmaceuticals Inc). IDrugs. 2000 Mar;3(3):336-45.
Ref 536340Metalloelastase (MMP-12) induced inflammatory response in mice airways: effects of dexamethasone, rolipram and marimastat. Eur J Pharmacol. 2007 Mar 15;559(1):75-81. Epub 2006 Dec 12.
Ref 536608Phase 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.
Ref 536723Pharmacoproteomics of a metalloproteinase hydroxamate inhibitor in breast cancer cells: dynamics of membrane type 1 matrix metalloproteinase-mediated membrane protein shedding. Mol Cell Biol. 2008 Aug;28(15):4896-914. Epub 2008 May 27.
Ref 536808Delayed administration of a matrix metalloproteinase inhibitor limits progressive brain injury after hypoxia-ischemia in the neonatal rat. J Neuroinflammation. 2008 Aug 11;5:34.
Ref 537040Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit. 2009 Feb;15(2):RA32-40.
Ref 537136Inhibition of gelatinase activity reduces neural injury in an ex vivo model of hypoxia-ischemia. Neuroscience. 2009 Jun 2;160(4):755-66. Epub 2009 Mar 9.
Ref 538064Matrix metalloproteinase inhibition as a novel anticancer strategy: a review with special focus on batimastat and marimastat. Pharmacol Ther. 1997;75(1):69-75.
Ref 551301Design, 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).

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