Target General Infomation
Target ID
T68251 (Former ID: TTDC00104)
Target Name
Matrix metalloproteinase-2 (MMP-2)
Synonyms
TBE-1; Matrix metalloproteinase 2; CLG4A; 72 kDa type IV collagenase; 72 kDa gelatinase
Gene Name
MMP2
Target Type
Successful target
[1]
Disease [+] 1 Target-related Diseases +
1 Lung cancer [ICD-11: 2C25]
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.
BioChemical Class
Peptidase
UniProt ID
MMP2_HUMAN
EC Number
EC 3.4.24.24
Sequence
MEALMARGALTGPLRALCLLGCLLSHAAAAPSPIIKFPGDVAPKTDKELAVQYLNTFYGC
PKESCNLFVLKDTLKKMQKFFGLPQTGDLDQNTIETMRKPRCGNPDVANYNFFPRKPKWD
KNQITYRIIGYTPDLDPETVDDAFARAFQVWSDVTPLRFSRIHDGEADIMINFGRWEHGD
GYPFDGKDGLLAHAFAPGTGVGGDSHFDDDELWTLGEGQVVRVKYGNADGEYCKFPFLFN
GKEYNSCTDTGRSDGFLWCSTTYNFEKDGKYGFCPHEALFTMGGNAEGQPCKFPFRFQGT
SYDSCTTEGRTDGYRWCGTTEDYDRDKKYGFCPETAMSTVGGNSEGAPCVFPFTFLGNKY
ESCTSAGRSDGKMWCATTANYDDDRKWGFCPDQGYSLFLVAAHEFGHAMGLEHSQDPGAL
MAPIYTYTKNFRLSQDDIKGIQELYGASPDIDLGTGPTPTLGPVTPEICKQDIVFDGIAQ
IRGEIFFFKDRFIWRTVTPRDKPMGPLLVATFWPELPEKIDAVYEAPQEEKAVFFAGNEY
WIYSASTLERGYPKPLTSLGLPPDVQRVDAAFNWSKNKKTYIFAGDKFWRYNEVKKKMDP
GFPKLIADAWNAIPDNLDAVVDLQGGGHSYFFKGAYYLKLENQSLKSVKFGSIKSDWLGC
Drugs and Modes of Action
Approved Drug(s) [+] 1 Approved Drugs +
1 Prinomastat Drug Info Approved Lung cancer [2], [3]
Clinical Trial Drug(s) [+] 4 Clinical Trial Drugs +
1 Epigallocatechin gallate Drug Info Phase 3 Hepatic fibrosis [4], [5], [6], [7]
2 Marimastat Drug Info Phase 3 Pancreatic cancer [8], [9]
3 Metastat Drug Info Phase 1 Acne vulgaris [10], [11]
4 Neovastat Drug Info Phase 1 Renal cell carcinoma [12]
Discontinued Drug(s) [+] 8 Discontinued Drugs +
1 BMS 275291 Drug Info Discontinued in Phase 3 Kaposi sarcoma [13]
2 Tanomastat Drug Info Discontinued in Phase 3 Osteoarthritis [14], [15]
3 Galarubicin Drug Info Discontinued in Phase 2 Solid tumour/cancer [16]
4 GM6001 Drug Info Discontinued in Phase 2 Corneal ulcer [17]
5 RS-130830 Drug Info Discontinued in Phase 2 Hepatitis C virus infection [18]
6 BB-1101 Drug Info Terminated Multiple sclerosis [20]
7 BB-3644 Drug Info Terminated Solid tumour/cancer [21]
8 CDP-845 Drug Info Terminated Solid tumour/cancer [22]
Preclinical Drug(s) [+] 1 Preclinical Drugs +
1 RO-26-2853 Drug Info Preclinical Solid tumour/cancer [19]
Mode of Action [+] 2 Modes of Action +
Inhibitor [+] 55 Inhibitor drugs +
1 Prinomastat Drug Info [1], [23], [24], [25], [26]
2 Epigallocatechin gallate Drug Info [27]
3 Marimastat Drug Info [28], [29], [30], [26]
4 Metastat Drug Info [31]
5 Neovastat Drug Info [32], [33], [34]
6 PMID29130358-Compound-Figure10(2a) Drug Info [35]
7 PMID29130358-Compound-Figure11(3) Drug Info [35]
8 PMID29130358-Compound-Figure13(4) Drug Info [35]
9 PMID29130358-Compound-Figure16(9a) Drug Info [35]
10 PMID29130358-Compound-Figure16(9b) Drug Info [35]
11 PMID29130358-Compound-Figure16(9c) Drug Info [35]
12 PMID29130358-Compound-Figure18(14) Drug Info [35]
13 PMID29130358-Compound-Figure18(14a) Drug Info [35]
14 PMID29130358-Compound-LonimacranthoideVII Drug Info [35]
15 PMID29130358-Compound-SB-3CT Drug Info [35]
16 BMS 275291 Drug Info [13], [36], [37], [26]
17 Tanomastat Drug Info [38], [39], [40], [26]
18 Galarubicin Drug Info [41]
19 GM6001 Drug Info [42]
20 RS-130830 Drug Info [43]
21 RO-26-2853 Drug Info [19]
22 BB-1101 Drug Info [44]
23 BB-3644 Drug Info [26], [21]
24 L-696418 Drug Info [46]
25 SC-44463 Drug Info [47]
26 (+/-)5-(biphenyl-4-yl)-3-hydroxypentanoic acid Drug Info [48]
27 2-(4'-chloro-biphenyl-4-sulfonyl)-pentanoic acid Drug Info [49]
28 2-(Biphenyl-4-ylsulfonyl)N-hydroxybenzamide Drug Info [50]
29 3-(4-(2-phenylethynyl)benzoyl)pentanoic acid Drug Info [51]
30 3-(4-Phenylethynylbenzoyl)nonanoic acid Drug Info [51]
31 4-(4-(dec-1-ynyl)phenyl)-4-oxobutanoic acid Drug Info [51]
32 5-(4-Phenoxy-phenyl)-pyrimidine-2,4,6-trione Drug Info [52]
33 5-Biphenyl-4-yl-5-ethyl-pyrimidine-2,4,6-trione Drug Info [52]
34 5-Biphenyl-4-yl-5-hexyl-pyrimidine-2,4,6-trione Drug Info [52]
35 5-Hexyl-5-phenyl-pyrimidine-2,4,6-trione Drug Info [52]
36 Cis-2-aminocyclohexylcarbamoylphosphonic acid Drug Info [53]
37 Clinopodic acid C Drug Info [54]
38 Folate gamma-hydroxamic acid Drug Info [55]
39 Folate gamma-L-proline-hydroxamic acid Drug Info [55]
40 IK-862 Drug Info [56]
41 Lithospermic acid Drug Info [54]
42 Methotrexate gamma-hydroxamic acid Drug Info [55]
43 Methotrexate gamma-L-proline-hydroxamic acid Drug Info [55]
44 MMI270 Drug Info [57]
45 N-Hydroxy-2-(4-phenoxy-benzenesulfonyl)benzamide Drug Info [50]
46 N-hydroxy-3-(2-oxo-2H-chromen-3-yl)propanamide Drug Info [58]
47 N-hydroxy-3-(6-methoxy-2-oxo-2H-chromen-3-yl) Drug Info [58]
48 PD-169469 Drug Info [59]
49 PNU-107859 Drug Info [60]
50 Ro-37-9790 Drug Info [61]
51 Roche 28-2653 Drug Info [62]
52 SC-74020 Drug Info [63]
53 SR-973 Drug Info [64]
54 UK-356618 Drug Info [47]
55 [2-(Biphenyl-4-sulfonyl)phenyl]acetic Acid Drug Info [50]
Modulator [+] 1 Modulator drugs +
1 CDP-845 Drug Info [45]
Target Regulators
Target-regulating microRNAs
Target-regulating Transcription Factors
Target-interacting Proteins
Target Profiles in Patients
Target Expression
 Profile (TEP)
Target Affiliated Biological Pathways
KEGG Pathway [+] 6 KEGG Pathways +
1 Leukocyte transendothelial migration
2 GnRH signaling pathway
3 Estrogen signaling pathway
4 Pathways in cancer
5 Proteoglycans in cancer
6 Bladder cancer
NetPath Pathway [+] 3 NetPath Pathways +
1 Leptin Signaling Pathway
2 TCR Signaling Pathway
3 ID Signaling Pathway
Panther Pathway [+] 1 Panther Pathways +
1 Alzheimer disease-presenilin pathway
PID Pathway [+] 11 PID Pathways +
1 LPA receptor mediated events
2 Plasma membrane estrogen receptor signaling
3 Osteopontin-mediated events
4 Validated transcriptional targets of AP1 family members Fra1 and Fra2
5 Angiopoietin receptor Tie2-mediated signaling
6 Direct p53 effectors
7 amb2 Integrin signaling
8 ATF-2 transcription factor network
9 FOXM1 transcription factor network
10 Regulation of nuclear beta catenin signaling and target gene transcription
11 Syndecan-2-mediated signaling events
Reactome [+] 5 Reactome Pathways +
1 Collagen degradation
2 Degradation of the extracellular matrix
3 Activation of Matrix Metalloproteinases
4 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
5 EPH-ephrin mediated repulsion of cells
WikiPathways [+] 3 WikiPathways +
1 Activation of Matrix Metalloproteinases
2 AGE/RAGE pathway
3 Matrix Metalloproteinases
Target-Related Models and Studies
Target Validation
Target QSAR Model
References
REF 1 AG-3340 (Agouron Pharmaceuticals Inc). IDrugs. 2000 Mar;3(3):336-45.
REF 2 URL: 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 3 Emerging therapies for neuropathic pain. Expert Opin Emerg Drugs. 2005 Feb;10(1):95-108.
REF 4 URL: 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: 7002).
REF 5 The green tea polyphenol (2)-epigallocatechin-3-gallate (EGCG) is not a beta-secretase inhibitor. Bioorg Med Chem Lett. 2012 Feb 1;22(3):1408-14.
REF 6 Epigallocatechin gallate modulates CYP450 isoforms in the female Swiss-Webster mouse. Toxicol Sci. 2003 Dec;76(2):262-70.
REF 7 Prolyl endopeptidase inhibitors from green tea. Arch Pharm Res. 2001 Aug;24(4):292-6.
REF 8 URL: 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 9 Randomized 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 10 ClinicalTrials.gov (NCT00001683) A Phase I Study of Oral COL-3 (NSC-683551), a Matrix Metalloproteinase Inhibitor, in Patients With Refractory Metastatic Cancer. U.S. National Institutes of Health.
REF 11 A phase I and pharmacokinetic study of Col-3 (Metastat), an oral tetracycline derivative with potent matrix metalloproteinase and antitumor properties. Clin Cancer Res. 2004 Oct 1;10(19):6512-21.
REF 12 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
REF 13 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.
REF 14 URL: 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: 6468).
REF 15 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010243)
REF 16 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004410)
REF 17 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001387)
REF 18 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010620)
REF 19 Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
REF 20 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006361)
REF 21 A 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 22 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006498)
REF 23 Inhibition of gelatinase activity reduces neural injury in an ex vivo model of hypoxia-ischemia. Neuroscience. 2009 Jun 2;160(4):755-66.
REF 24 Delayed 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 25 Pharmacoproteomics of a metalloproteinase hydroxamate inhibitor in breast cancer cells: dynamics of membrane type 1 matrix metalloproteinase-mediat... Mol Cell Biol. 2008 Aug;28(15):4896-914.
REF 26 Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat Rev Cancer. 2006 Mar;6(3):227-39.
REF 27 Regioselective synthesis of methylated epigallocatechin gallate via nitrobenzenesulfonyl (Ns) protecting group. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4171-4.
REF 28 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.
REF 29 Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit. 2009 Feb;15(2):RA32-40.
REF 30 Matrix metalloproteinase inhibition as a novel anticancer strategy: a review with special focus on batimastat and marimastat. Pharmacol Ther. 1997;75(1):69-75.
REF 31 Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer. 2002 Sep;2(9):657-72.
REF 32 Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol. 2001 Dec;28(6):620-5.
REF 33 Neovastat (AE-941) inhibits the airway inflammation and hyperresponsiveness in a murine model of asthma. J Microbiol. 2005 Feb;43(1):11-6.
REF 34 The effect of Neovastat (AE-941) on an experimental metastatic bone tumor model. Int J Oncol. 2002 Feb;20(2):299-303.
REF 35 Gelatinase inhibitors: a patent review (2011-2017).Expert Opin Ther Pat. 2018 Jan;28(1):31-46.
REF 36 Randomized 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 37 Randomized 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 38 Radiation therapy and biological compounds for consolidation therapy in advanced ovarian cancer. Int J Gynecol Cancer. 2008 Mar-Apr;18 Suppl 1:44-6.
REF 39 Conflicting results from clinical observations and murine models: what is the role of plasminogen activators in tumor growth J Natl Cancer Inst. 2006 Jun 7;98(11):726-7.
REF 40 A phase III randomized trial of BAY 12-9566 (tanomastat) as maintenance therapy in patients with advanced ovarian cancer responsive to primary surg... Gynecol Oncol. 2006 Aug;102(2):300-8.
REF 41 Inhibitory effect of DA-125, a new anthracyclin analog antitumor agent, on the invasion of human fibrosarcoma cells by down-regulating the matrix m... Biochem Pharmacol. 2005 Dec 19;71(1-2):21-31.
REF 42 Introduction of the 4-(4-bromophenyl)benzenesulfonyl group to hydrazide analogs of Ilomastat leads to potent gelatinase B (MMP-9) inhibitors with i... Bioorg Med Chem. 2008 Sep 15;16(18):8745-59.
REF 43 Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13). Bioorg Med Chem Lett. 2005 Feb 15;15(4):1101-6.
REF 44 Broad spectrum matrix metalloproteinase inhibitors: an examination of succinamide hydroxamate inhibitors with P1 C alpha gem-disubstitution. Bioorg Med Chem Lett. 1998 Jun 16;8(12):1443-8.
REF 45 Clinical potential of matrix metalloprotease inhibitors. Drugs R D. 1999 Feb;1(2):117-29.
REF 46 Inhibition of matrix metalloproteinases by N-carboxyalkyl peptides containing extended alkyl residues At P1', Bioorg. Med. Chem. Lett. 5(6):539-542 (1995).
REF 47 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.
REF 48 The identification of beta-hydroxy carboxylic acids as selective MMP-12 inhibitors. Bioorg Med Chem Lett. 2009 Oct 1;19(19):5760-3.
REF 49 Synthesis and SAR of alpha-sulfonylcarboxylic acids as potent matrix metalloproteinase inhibitors. Bioorg Med Chem Lett. 2006 Jun 15;16(12):3096-100.
REF 50 Design, synthesis, biological evaluation, and NMR studies of a new series of arylsulfones as selective and potent matrix metalloproteinase-12 inhib... J Med Chem. 2009 Oct 22;52(20):6347-61.
REF 51 Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted gamma-keto carboxylic acids. J Med Chem. 2006 Jan 26;49(2):456-8.
REF 52 Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors. Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.
REF 53 Carbamoylphosphonate matrix metalloproteinase inhibitors 6: cis-2-aminocyclohexylcarbamoylphosphonic acid, a novel orally active antimetastatic mat... J Med Chem. 2008 Mar 13;51(5):1406-14.
REF 54 Matrix metalloproteinase-2 inhibitors from Clinopodium chinense var. parviflorum. J Nat Prod. 2009 Aug;72(8):1379-84.
REF 55 Methotrexate gamma-hydroxamate derivatives as potential dual target antitumor drugs. Bioorg Med Chem. 2007 Feb 1;15(3):1266-74.
REF 56 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.
REF 57 Picking the S1, S1' and S2' pockets of matrix metalloproteinases. A niche for potent acyclic sulfonamide inhibitors. Bioorg Med Chem Lett. 1999 Jun 21;9(12):1691-6.
REF 58 Chromen-based TNF-alpha converting enzyme (TACE) inhibitors: design, synthesis, and biological evaluation. Bioorg Med Chem. 2008 Jan 1;16(1):530-5.
REF 59 Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates. J Med Chem. 2006 Feb 9;49(3):923-31.
REF 60 A molecular basis for the selectivity of thiadiazole urea inhibitors with stromelysin-1 and gelatinase-A from generalized born molecular dynamics s... J Med Chem. 2004 Jun 3;47(12):3065-74.
REF 61 11,21-Bisphenyl-19-norpregnane derivatives are selective antiglucocorticoids, Bioorg. Med. Chem. Lett. 7(17):2299-2302 (1997).
REF 62 The new synthetic matrix metalloproteinase inhibitor (Roche 28-2653) reduces tumor growth and prolongs survival in a prostate cancer standard rat model. Oncogene. 2002 Mar 27;21(13):2089-96.
REF 63 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
REF 64 Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors. Bioorg Med Chem Lett. 2006 May 1;16(9):2357-63.

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