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MMP14

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Target id: 1638

Nomenclature: MMP14

Family: M10: Matrix metallopeptidase

Contents:

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
Alphafold P50281 (Hs), P53690 (Mm), Q10739 (Rn)
BRENDA 3.4.24.80
CATH/Gene3D 3.40.390.10, 2.110.10.10
ChEMBL Target CHEMBL3869 (Hs), CHEMBL4295783 (Mm)
DrugBank Target P50281 (Hs)
Ensembl Gene ENSG00000157227 (Hs), ENSMUSG00000000957 (Mm), ENSRNOG00000010947 (Rn)
Entrez Gene 4323 (Hs), 17387 (Mm), 81707 (Rn)
Human Protein Atlas ENSG00000157227 (Hs)
KEGG Enzyme 3.4.24.80
KEGG Gene hsa:4323 (Hs), mmu:17387 (Mm), rno:81707 (Rn)
OMIM 600754 (Hs)
Orphanet ORPHA314731 (Hs)
Pharos P50281 (Hs)
RefSeq Nucleotide NM_004995 (Hs), NM_008608 (Mm), NM_031056 (Rn)
RefSeq Protein NP_004986 (Hs), NP_032634 (Mm), NP_112318 (Rn)
UniProtKB P50281 (Hs), P53690 (Mm), Q10739 (Rn)
Wikipedia MMP14 (Hs)
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 – 9.0 pIC50 4,9
⤷ pIC50 9.0 (IC50 1.1x10-9 M) [9]
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]
TP0556351 Peptide Click here for species-specific activity table Hs Inhibition 5.7 pIC50 9
⤷ pIC50 5.7 (IC50 2.216x10-6 M) [9]
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)
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Cellular signalling
Immuno Process:  Inflammation
Immuno Process:  Chemotaxis & migration
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]

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]

How to cite this page

M10: Matrix metallopeptidase: MMP14. Last modified on 12/07/2022. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1638.