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Molecule Details

General Information of the Molecule
Name
Matrix metalloproteinase-2 (MMP-2)
Synonyms
TBE-1; Matrix metalloproteinase 2; CLG4A; 72 kDa type IV collagenase; 72 kDa gelatinase
Gene Name
MMP2
Gene ID
4313
Sequence
MEALMARGALTGPLRALCLLGCLLSHAAAAPSPIIKFPGDVAPKTDKELAVQYLNTFYGC
PKESCNLFVLKDTLKKMQKFFGLPQTGDLDQNTIETMRKPRCGNPDVANYNFFPRKPKWD
KNQITYRIIGYTPDLDPETVDDAFARAFQVWSDVTPLRFSRIHDGEADIMINFGRWEHGD
GYPFDGKDGLLAHAFAPGTGVGGDSHFDDDELWTLGEGQVVRVKYGNADGEYCKFPFLFN
GKEYNSCTDTGRSDGFLWCSTTYNFEKDGKYGFCPHEALFTMGGNAEGQPCKFPFRFQGT
SYDSCTTEGRTDGYRWCGTTEDYDRDKKYGFCPETAMSTVGGNSEGAPCVFPFTFLGNKY
ESCTSAGRSDGKMWCATTANYDDDRKWGFCPDQGYSLFLVAAHEFGHAMGLEHSQDPGAL
MAPIYTYTKNFRLSQDDIKGIQELYGASPDIDLGTGPTPTLGPVTPEICKQDIVFDGIAQ
IRGEIFFFKDRFIWRTVTPRDKPMGPLLVATFWPELPEKIDAVYEAPQEEKAVFFAGNEY
WIYSASTLERGYPKPLTSLGLPPDVQRVDAAFNWSKNKKTYIFAGDKFWRYNEVKKKMDP
GFPKLIADAWNAIPDNLDAVVDLQGGGHSYFFKGAYYLKLENQSLKSVKFGSIKSDWLGC
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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.
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Uniprot ID
MMP2_HUMAN
EC Number
EC: 3.4.24.24
Pfam
PF00040 ; PF00045 ; PF00413 ; PF01471
KEGG ID
hsa4313
TTD ID
T68251
INTEDE ID
DME0561
A List of Drug Combination(s) Able to Regulate This Molecule
          Expression Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Expression of This Molecule [1]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Quercetin   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 2 Down-regulating the Expression of This Molecule [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Fisetin   NP Info  + Sorafenib   Drug Info 
                    Structure +
                    Drug Combination 3 Down-regulating the Expression of This Molecule [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Triptolide   NP Info  + AMD3100   Drug Info 
                    Structure +
                    Drug Combination 4 Down-regulating the Expression of This Molecule [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Docetaxel   Drug Info 
                    Structure +
                    Drug Combination 5 Down-regulating the Expression of This Molecule [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Epigallocatechin gallate   NP Info  + 6-OH-11-O-Hydroxyphenanthrene   Drug Info 
                    Structure +
                    Drug Combination 6 Down-regulating the Expression of This Molecule [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Vicenin-2   NP Info  + Radiation   Drug Info 
                    Structure +
                    Drug Combination 7 Down-regulating the Expression of This Molecule [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Epigallocatechin gallate   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 8 Down-regulating the Expression of This Molecule [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Fisetin   NP Info  + Cabazitaxel   Drug Info 
                    Structure +
                    Drug Combination 9 Down-regulating the Expression of This Molecule [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Epigallocatechin gallate   NP Info  + Celecoxib   Drug Info 
                    Structure +
                    Drug Combination 10 Down-regulating the Expression of This Molecule [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ginsenoside Rg3   NP Info  + Endostar   Drug Info 
                    Structure +
                    Drug Combination 11 Down-regulating the Expression of This Molecule [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 12 Down-regulating the Expression of This Molecule [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Carboplatin   Drug Info 
                    Structure +
                    Drug Combination 13 Down-regulating the Expression of This Molecule [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 14 Down-regulating the Expression of This Molecule [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Eugenol   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 15 Down-regulating the Expression of This Molecule [15]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Flavopiridol   NP Info  + Vorinostat   Drug Info 
                    Structure +
                    Drug Combination 16 Down-regulating the Expression of This Molecule [16]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Canstatin   Drug Info 
                    Structure +
                    Drug Combination 17 Down-regulating the Expression of This Molecule [17]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Heparin   NP Info  + X-ray irradiation   Drug Info 
                    Structure +
                    Drug Combination 18 Down-regulating the Expression of This Molecule [18]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Dehydrocostus lactone   NP Info  + Doxorubicin   Drug Info 
                    Structure +
                    Drug Combination 19 Down-regulating the Expression of This Molecule [19]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Shikonin   NP Info  + Temozolomide   Drug Info 
                    Structure +
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Expression of This Molecule [20]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Genistein   NP Info  + Cisplatin   Drug Info 
                    Structure +
Natural Product(s) of This Target
1 Epigallocatechin gallate  NP Info  Phase 3 Hamamelis virginiana
References
Reference 1 Effects of Quercetin on the Efficacy of Various Chemotherapeutic Drugs in Cervical Cancer Cells. Drug Des Devel Ther. 2021 Feb 15;15:577-588.
Reference 2 Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells. Oncotarget. 2015 Sep 29;6(29):28296-311.
Reference 3 AMD3100 combined with triptolide inhibit proliferation, invasion and metastasis and induce apoptosis of human U2OS osteosarcoma cells. Biomed Pharmacother. 2017 Feb;86:677-685.
Reference 4 Curcumin enhances anti?cancer efficacy of either gemcitabine or docetaxel on pancreatic cancer cells. Oncol Rep. 2020 Oct;44(4):1393-1402.
Reference 5 Epigallocatechin-3-gallate and 6-OH-11-O-Hydroxyphenanthrene Limit BE(2)-C Neuroblastoma Cell Growth and Neurosphere Formation In Vitro. Nutrients. 2018 Aug 22;10(9):1141.
Reference 6 Vicenin-2: a potential radiosensitizer of non-small cell lung cancer cells. Mol Biol Rep. 2018 Oct;45(5):1219-1225.
Reference 7 Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis. Oncogene. 2008 Mar 27;27(14):2055-63.
Reference 8 Fisetin Enhances Chemotherapeutic Effect of Cabazitaxel against Human Prostate Cancer Cells. Mol Cancer Ther. 2016 Dec;15(12):2863-2874.
Reference 9 (-)-Epigallocatechin-3-gallate, a green tea-derived catechin, synergizes with celecoxib to inhibit IL-1-induced tumorigenic mediators by human pancreatic adenocarcinoma cells Colo357. Eur J Pharmacol. 2012 Jun 5;684(1-3):36-43.
Reference 10 Inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice. Asian Pac J Trop Med. 2016 Feb;9(2):180-3.
Reference 11 Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res. 2007 Apr 15;67(8):3853-61.
Reference 12 Curcumin sensitizes human lung cancer cells to apoptosis and metastasis synergistically combined with carboplatin. Exp Biol Med (Maywood). 2015 Nov;240(11):1416-25.
Reference 13 Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5). Carcinogenesis. 2005 Nov;26(11):1905-13.
Reference 14 Eugenol potentiates cisplatin anti-cancer activity through inhibition of ALDH-positive breast cancer stem cells and the NF-kappaB signaling pathway. Mol Carcinog. 2018 Mar;57(3):333-346.
Reference 15 Combination of vorinostat and flavopiridol is selectively cytotoxic to multidrug-resistant neuroblastoma cell lines with mutant TP53. Mol Cancer Ther. 2010 Dec;9(12):3289-301.
Reference 16 Combination of canstatin and arsenic trioxide suppresses the development of hepatocellular carcinoma. Drug Dev Res. 2021 May;82(3):430-439.
Reference 17 Combination of nadroparin with radiotherapy results in powerful synergistic antitumor effects in lung adenocarcinoma A549 cells. Oncol Rep. 2016 Oct;36(4):2200-6.
Reference 18 Dehydrocostus Lactone Enhances Chemotherapeutic Potential of Doxorubicin in Lung Cancer by Inducing Cell Death and Limiting Metastasis. Med Sci Monit. 2018 Nov 2;24:7850-7861.
Reference 19 Dual treatment with shikonin and temozolomide reduces glioblastoma tumor growth, migration and glial-to-mesenchymal transition. Cell Oncol (Dordr). 2017 Jun;40(3):247-261.
Reference 20 Synergistic action of genistein and cisplatin on growth inhibition and cytotoxicity of human medulloblastoma cells. Pediatr Neurosurg. 2000 Sep;33(3):123-31.
Reference 21 Regioselective synthesis of methylated epigallocatechin gallate via nitrobenzenesulfonyl (Ns) protecting group. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4171-4.
Cite NPCDR
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Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China