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MMP2

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1629

Nomenclature: MMP2

Family: M10: Matrix metallopeptidase

This target is also described as a ligand entry: matrix metalloproteinase 2; matrix metalloproteinase 2; matrix metalloproteinase 2

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 660 16q12.2 MMP2 matrix metallopeptidase 2
Mouse - 662 8 44.99 cM Mmp2 matrix metallopeptidase 2
Rat - 662 19p11 Mmp2 matrix metallopeptidase 2
Previous and Unofficial Names Click here for help
TBE- 1 | gelatinase A | CLG4 | CLG4A | matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase)
Database Links Click here for help
Specialist databases
MEROPS M10.003 (Hs)
Other databases
Alphafold P08253 (Hs), P33434 (Mm), P33436 (Rn)
BRENDA 3.4.24.24
CATH/Gene3D 2.10.10.10, 2.110.10.10, 3.40.390.10, 1.10.101.10
ChEMBL Target CHEMBL333 (Hs), CHEMBL3095 (Mm), CHEMBL1075175 (Rn)
DrugBank Target P08253 (Hs)
Ensembl Gene ENSG00000087245 (Hs), ENSMUSG00000031740 (Mm), ENSRNOG00000016695 (Rn)
Entrez Gene 4313 (Hs), 17390 (Mm), 81686 (Rn)
Human Protein Atlas ENSG00000087245 (Hs)
KEGG Enzyme 3.4.24.24
KEGG Gene hsa:4313 (Hs), mmu:17390 (Mm), rno:81686 (Rn)
OMIM 120360 (Hs)
Orphanet ORPHA123439 (Hs)
Pharos P08253 (Hs)
RefSeq Nucleotide NM_004530 (Hs), NM_001127891 (Hs), NM_008610 (Mm), NM_031054 (Rn)
RefSeq Protein NP_004521 (Hs), NP_001121363 (Hs), NP_032636 (Mm), NP_112316 (Rn)
UniProtKB P08253 (Hs), P33434 (Mm), P33436 (Rn)
Wikipedia MMP2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human MMP-2 catalytic domain in complex with inhibitor
PDB Id:  7XJO
Ligand:  TP0556351
Resolution:  2.0Å
Species:  Human
References:  9
Enzyme Reaction Click here for help
EC Number: 3.4.24.24

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
tanomastat Small molecule or natural product Hs Inhibition 8.0 pKi 3
⤷ pKi 8.0 (Ki 1x10-8 M) [3]
SB-3CT Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.9 pKi 1
⤷ pKi 7.9 (Ki 1.39x10-8 M) [1]
(R)-ND-336 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.9 pKi 6
⤷ pKi 6.9 (Ki 1.27x10-7 M) [6]
TP0556351 Peptide Click here for species-specific activity table Hs Inhibition 9.7 pIC50 9
⤷ pIC50 9.7 (IC50 2x10-10 M) [9]
ilomastat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 – 9.7 pIC50 4,9
⤷ pIC50 9.7 (IC50 1.9x10-10 M) [9]
pIC50 8.1 (IC50 7x10-9 M) [4]
AZD6605 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.5 pIC50 5
⤷ pIC50 8.5 (IC50 3x10-9 M) [5]
marimastat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pIC50 8
⤷ pIC50 8.2 (IC50 6x10-9 M) [8]
CGS-27023A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pIC50 7
⤷ pIC50 7.6 (IC50 2.5x10-8 M) [7]
tiludronic acid Small molecule or natural product Approved drug Hs Inhibition 5.1 pIC50 10
⤷ pIC50 5.1 (IC50 7.2x10-6 M) [10]
ARP100 Small molecule or natural product Ligand has a PDB structure Hs Inhibition - - 11
⤷ [11]
Immunopharmacology Comments
MMP2 is included in GtoImmuPdb based on its potential involvement in asthma.
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
Immuno Process:  Immune regulation
Immuno Process:  Inflammation
Immuno Disease Associations
Disease Name:  Asthma
Disease Synonyms:  no synonynms
Comment:  MMP2 and MMP9 can promote the egress of inflammatory cells into airway lumen, suggesting a protective anti-inflammatory role in asthma. MMP2/MMP9 gelatinolytic activity is elevated in the sputum of asthmatic patients
Disease X-refs:  Disease Ontology: DOID:2841
OMIM: 600807
References:  2
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Multicentric osteolysis, nodulosis, and arthropathy
Synonyms: Nodulosis-arthropathy-osteolysis syndrome [Orphanet: ORPHA85196]
OMIM: 259600
Orphanet: ORPHA85196
Disease:  Winchester syndrome
OMIM: 277950
Orphanet: ORPHA3460
General Comments
Matrix metalloproteinase-2 (MMP2) is a zinc-dependent endopeptidase that degrades extracellular matrix proteins. It is being explored as a drug target in cancer, arthritis, and fibrosis. Selective inhibitors are in development.

References

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1. Brown S, Bernardo MM, Li Z-H, Kotra LP, Tanaka Y, Fridman R, Mobashery S. (2000) Potent and Selective Mechanism-Based Inhibition of Gelatinases. J Am Chem Soc, 122: 6799-6800.

2. Cataldo D, Munaut C, Noël A, Frankenne F, Bartsch P, Foidart JM, Louis R. (2000) MMP-2- and MMP-9-linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease. Int Arch Allergy Immunol, 123 (3): 259-67. [PMID:11112863]

3. Fisher JF, Mobashery S. (2006) Recent advances in MMP inhibitor design. Cancer Metastasis Rev, 25 (1): 115-36. [PMID:16680577]

4. Ma D, Wu W, Yang G, Li J, Li J, Ye Q. (2004) Tetrahydroisoquinoline based sulfonamide hydroxamates as potent matrix metalloproteinase inhibitors. Bioorg Med Chem Lett, 14 (1): 47-50. [PMID:14684295]

5. MRC. AZD6605 Matrix metallopeptidase 13 (MMP13) inhibitor. Accessed on 28/10/2014. Modified on 28/10/2014. MRC/AstraZeneca: Mechanisms of Disease Call, http://webarchive.nationalarchives.gov.uk/20120104105854/http://www.mrc.ac.uk/consumption/groups/public/documents/content/mrc008371.pdf

6. Nguyen TT, Ding D, Wolter WR, Pérez RL, Champion MM, Mahasenan KV, Hesek D, Lee M, Schroeder VA, Jones JI et al.. (2018) Validation of Matrix Metalloproteinase-9 (MMP-9) as a Novel Target for Treatment of Diabetic Foot Ulcers in Humans and Discovery of a Potent and Selective Small-Molecule MMP-9 Inhibitor That Accelerates Healing. J Med Chem, 61 (19): 8825-8837. [PMID:30212201]

7. Nuti E, Casalini F, Santamaria S, Gabelloni P, Bendinelli S, Da Pozzo E, Costa B, Marinelli L, La Pietra V, Novellino E et al.. (2011) Synthesis and biological evaluation in U87MG glioma cells of (ethynylthiophene)sulfonamido-based hydroxamates as matrix metalloproteinase inhibitors. Eur J Med Chem, 46 (7): 2617-29. [PMID:21514700]

8. Rasmussen HS, McCann PP. (1997) Matrix metalloproteinase inhibition as a novel anticancer strategy: a review with special focus on batimastat and marimastat. Pharmacol Ther, 75 (1): 69-75. [PMID:9364582]

9. Takeuchi T, Hayashi M, Tamita T, Nomura Y, Kojima N, Mitani A, Takeda T, Hitaka K, Kato Y, Kamitani M et al.. (2022) Discovery of Aryloxyphenyl-Heptapeptide Hybrids as Potent and Selective Matrix Metalloproteinase-2 Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis. J Med Chem, 65 (12): 8493-8510. [PMID:35687819]

10. Tauro M, Laghezza A, Loiodice F, Agamennone M, Campestre C, Tortorella P. (2013) Arylamino methylene bisphosphonate derivatives as bone seeking matrix metalloproteinase inhibitors. Bioorg Med Chem, 21 (21): 6456-65. [PMID:24071448]

11. Tuccinardi T, Martinelli A, Nuti E, Carelli P, Balzano F, Uccello-Barretta G, Murphy G, Rossello A. (2006) Amber force field implementation, molecular modelling study, synthesis and MMP-1/MMP-2 inhibition profile of (R)- and (S)-N-hydroxy-2-(N-isopropoxybiphenyl-4-ylsulfonamido)-3-methylbutanamides. Bioorg Med Chem, 14 (12): 4260-76. [PMID:16483784]

How to cite this page

M10: Matrix metallopeptidase: MMP2. Last modified on 12/07/2022. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1629.