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MMP14

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1638

Nomenclature: MMP14

Family: M10: Matrix metallopeptidase

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 582 14q11.2 MMP14 matrix metallopeptidase 14
Mouse 1 582 14 27.79 cM Mmp14 matrix metallopeptidase 14 (membrane-inserted)
Rat 1 582 15p13 Mmp14 matrix metallopeptidase 14
Previous and Unofficial Names Click here for help
MMP- X1 | membrane type 1 metalloprotease | membrane-type matrix metalloproteinase 1 | MT1MMP | MTMMP1 | Membrane type 1-MMP | matrix metallopeptidase 14 (membrane-inserted)
Database Links Click here for help
Specialist databases
MEROPS M10.014 (Hs)
Other databases
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 3.4.24.80

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
compound 29e [PMID: 23631440] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pKi 2
pKi 8.4 (Ki 4x10-9 M) [2]
(R)-ND-336 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.9 pKi 5
pKi 6.9 (Ki 1.19x10-7 M) [5]
ilomastat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pIC50 4
pIC50 7.6 (IC50 2.3x10-8 M) [4]
CGS-27023A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pIC50 6
pIC50 7.6 (IC50 2.3x10-8 M) [6]
Immunopharmacology Comments
MMP14 is included in GtoImmuPdb based on its contribution to degradation of collagenous cartilage matrix in rheumatoid arthritis. An anti-MMP14 antibody, DX-2400 [1], has shown preclinical efficacy in the mouse collagen-induced arthritis (CIA) model of RA [3]. DX-2400 inhibits MMP14 activity with a Ki of 0.8 nM [1].
Immuno Process Associations
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0045579 positive regulation of B cell differentiation ISS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0045579 positive regulation of B cell differentiation ISS
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GO:1905523 positive regulation of macrophage migration IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:0045579 positive regulation of B cell differentiation ISS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0045579 positive regulation of B cell differentiation ISS
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:1905523 positive regulation of macrophage migration IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:1905523 positive regulation of macrophage migration IEA
Immuno Disease Associations
Disease Name:  Rheumatoid arthritis
Disease Synonyms:  no synonynms
Comment:  MMP14 (also called MT1-MMP) is highly expressed in fibroblast-like synoviocytes and macrophages from patients with RA, and is reckoned to be one of the main MMPs involved in degradation of collagenous cartilage matrix
Disease X-refs:  Disease Ontology: DOID:7148
OMIM: 180300
References:  7-8
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

References

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1. Devy L, Huang L, Naa L, Yanamandra N, Pieters H, Frans N, Chang E, Tao Q, Vanhove M, Lejeune A et al.. (2009) Selective inhibition of matrix metalloproteinase-14 blocks tumor growth, invasion, and angiogenesis. Cancer Res, 69 (4): 1517-26. [PMID:19208838]

2. Jin Y, Roycik MD, Bosco DB, Cao Q, Constantino MH, Schwartz MA, Sang QX. (2013) Matrix metalloproteinase inhibitors based on the 3-mercaptopyrrolidine core. J Med Chem, 56 (11): 4357-73. [PMID:23631440]

3. Kaneko K, Williams RO, Dransfield DT, Nixon AE, Sandison A, Itoh Y. (2016) Selective Inhibition of Membrane Type 1 Matrix Metalloproteinase Abrogates Progression of Experimental Inflammatory Arthritis: Synergy With Tumor Necrosis Factor Blockade. Arthritis Rheumatol, 68 (2): 521-31. [PMID:26315469]

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. 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]

6. 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]

7. Pap T, Shigeyama Y, Kuchen S, Fernihough JK, Simmen B, Gay RE, Billingham M, Gay S. (2000) Differential expression pattern of membrane-type matrix metalloproteinases in rheumatoid arthritis. Arthritis Rheum, 43 (6): 1226-32. [PMID:10857781]

8. Sabeh F, Fox D, Weiss SJ. (2010) Membrane-type I matrix metalloproteinase-dependent regulation of rheumatoid arthritis synoviocyte function. J Immunol, 184 (11): 6396-406. [PMID:20483788]

How to cite this page

M10: Matrix metallopeptidase: MMP14. Last modified on 22/05/2020. Accessed on 16/04/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1638.