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MMP13

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Target id: 1637

Nomenclature: MMP13

Family: M10: Matrix metallopeptidase

This target is also described as a ligand entry: matrix metalloproteinase 13

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 471 11q22.2 MMP13 matrix metallopeptidase 13
Mouse - 472 9 A1 Mmp13 matrix metallopeptidase 13
Rat - 466 8q11 Mmp13 matrix metallopeptidase 13
Previous and Unofficial Names Click here for help
UMRCASE | interstitial collagenase | Mmp1 | CLG3 | collagenase-1 | matrix metallopeptidase 13 (collagenase 3)
Database Links Click here for help
Specialist databases
MEROPS M10.013 (Hs)
Other databases
Alphafold P45452 (Hs), P33435 (Mm), P23097 (Rn)
BRENDA 3.4.24.-
CATH/Gene3D 3.40.390.10, 2.110.10.10
ChEMBL Target CHEMBL280 (Hs), CHEMBL3638350 (Mm), CHEMBL4944 (Rn)
DrugBank Target P45452 (Hs), P45452 (Hs)
Ensembl Gene ENSG00000137745 (Hs), ENSMUSG00000050578 (Mm), ENSRNOG00000008478 (Rn)
Entrez Gene 4322 (Hs), 17386 (Mm), 171052 (Rn)
Human Protein Atlas ENSG00000137745 (Hs)
KEGG Enzyme 3.4.24.-
KEGG Gene hsa:4322 (Hs), mmu:17386 (Mm), rno:171052 (Rn)
OMIM 600108 (Hs)
Orphanet ORPHA123436 (Hs)
Pharos P45452 (Hs)
RefSeq Nucleotide NM_002427 (Hs), NM_008607 (Mm), NM_133530 (Rn)
RefSeq Protein NP_002418 (Hs), NP_032633 (Mm), NP_598214 (Rn)
SynPHARM 82515 (in complex with compound 15 [PMID: 22017539])
78451 (in complex with compound 1 [PMID: 17935984])
UniProtKB P45452 (Hs), P33435 (Mm), P23097 (Rn)
Wikipedia MMP13 (Hs)
Enzyme Reaction Click here for help
EC Number: 3.4.24.-

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
SL422 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.4 pKi 15
⤷ pKi 9.4 (Ki 4.5x10-10 M) [15]
prinomastat Small molecule or natural product Ligand has a PDB structure Hs Inhibition 10.4 pIC50 1
⤷ pIC50 10.4 (IC50 3.8x10-11 M) [1]
ilomastat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.6 pIC50 11
⤷ pIC50 9.6 (IC50 2.8x10-10 M) [11]
compound 1 [PMID: 17935984] Small molecule or natural product Ligand has a PDB structure Hs Inhibition 9.2 pIC50 6
⤷ pIC50 9.2 (IC50 6x10-10 M) [6]
compound 15 [PMID: 22017539] Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 9.0 pIC50 12
⤷ pIC50 9.0 (IC50 1x10-9 M) [12]
PF-152 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 8.8 pIC50 10
⤷ pIC50 8.8 (IC50 1.5x10-9 M) [10]
marimastat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pIC50 2
⤷ pIC50 8.7 (IC50 2x10-9 M) [2]
batimastat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.3 pIC50 5
⤷ pIC50 8.3 (IC50 5x10-9 M) [5]
AZD6605 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.3 pIC50 9
⤷ pIC50 8.3 (IC50 5x10-9 M) [9]
apratastat Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.1 pIC50 8
⤷ pIC50 8.1 (IC50 8x10-9 M) [8]
MMP13 tracer [18F]5j Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Inhibition 7.8 pIC50 2
⤷ pIC50 7.8 (IC50 1.6x10-8 M) [2]
Description: Inhibitor potency against human recombinant MMP13, determined using the fluorogenic substrate Mca-Lys-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2
[18F]FMBP Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Inhibition 7.3 pIC50 3
⤷ pIC50 7.3 (IC50 5.6x10-8 M) [3]
TP0556351 Peptide Click here for species-specific activity table Hs Inhibition 6.8 pIC50 11
⤷ pIC50 6.8 (IC50 1.74x10-7 M) [11]
CL82198 Small molecule or natural product Hs Inhibition - - 4
⤷ [4]
WAY170523 Small molecule or natural product Hs Inhibition - - 4
⤷ [4]
Inhibitor Comments
SL422 is a broad-spectrum inhibitor of MMP enzymes [15].
Immunopharmacology Comments
Elevated MMP13 expression correlates with inflammation in patients with Crohn's disease and ulcerative colitis, suggesting a role for this protease in disease pathogenesis [14]. Inhibition of MMP13's preferential degradation of type II collagen and aggrecan is predicted to prevent/reduce the destruction of cartilage in rheumatoid arthritis [7,16].
Immuno Disease Associations
Disease Name:  Osteoarthritis
Disease Synonyms:  no synonynms
Comment:  The collagenolytic MMPs 3 and 13 are strongly implicated in cartilage destruction in OA.
Disease X-refs:  Disease Ontology: DOID:8398
References:  13
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Spondyloepimetaphyseal dysplasia, Missouri type
Synonyms: Metaphyseal anadysplasia [Orphanet: ORPHA1040]
Metaphyseal anadysplasia 1
Disease Ontology: DOID:0080030
OMIM: 602111
Orphanet: ORPHA93356, ORPHA1040

References

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1. Abbenante G, Fairlie DP. (2005) Protease inhibitors in the clinic. Med Chem, 1 (1): 71-104. [PMID:16789888]

2. Buchler A, Ismailani US, MacMullin N, Abdirahman F, Adi M, Bi C, Jany C, Keillor JW, Rotstein BH. (2023) Quinazoline-2-Carboxamides as Selective PET Radiotracers for Matrix Metalloproteinase-13 Imaging in Atherosclerosis. J Med Chem, 66 (10): 6682-6696. [PMID:37158732]

3. Buchler A, Munch M, Farber G, Zhao X, Al-Haddad R, Farber E, Rotstein BH. (2022) Selective Imaging of Matrix Metalloproteinase-13 to Detect Extracellular Matrix Remodeling in Atherosclerotic Lesions. Mol Imaging Biol, 24 (1): 93-103. [PMID:34231104]

4. Chen JM, Nelson FC, Levin JI, Mobilio D, Moy FJ, Nilakantan R, Zask A, Powers R. (2000) Structure-Based Design of a Novel, Potent, and Selective Inhibitor for MMP-13 Utilizing NMR Spectroscopy and Computer-Aided Molecular Design. J Am Chem Soc, 122 (40): 9648-9654. DOI: 10.1021/ja001547g

5. Fray MJ, Dickinson RP, Huggins JP, Occleston NL. (2003) A potent, selective inhibitor of matrix metalloproteinase-3 for the topical treatment of chronic dermal ulcers. J Med Chem, 46 (16): 3514-25. [PMID:12877590]

6. Freeman-Cook KD, Reiter LA, Noe MC, Antipas AS, Danley DE, Datta K, Downs JT, Eisenbeis S, Eskra JD, Garmene DJ et al.. (2007) Potent, selective spiropyrrolidine pyrimidinetrione inhibitors of MMP-13. Bioorg Med Chem Lett, 17 (23): 6529-34. [PMID:17935984]

7. Konttinen YT, Ainola M, Valleala H, Ma J, Ida H, Mandelin J, Kinne RW, Santavirta S, Sorsa T, López-Otín C et al.. (1999) Analysis of 16 different matrix metalloproteinases (MMP-1 to MMP-20) in the synovial membrane: different profiles in trauma and rheumatoid arthritis. Ann Rheum Dis, 58 (11): 691-7. [PMID:10531073]

8. Levin JI, Chen JM, Laakso LM, Du M, Schmid J, Xu W, Cummons T, Xu J, Jin G, Barone D et al.. (2006) Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates. Bioorg Med Chem Lett, 16 (6): 1605-9. [PMID:16426848]

9. 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

10. Ruminski PG, Massa M, Strohbach J, Hanau CE, Schmidt M, Scholten JA, Fletcher TR, Hamper BC, Carroll JN, Shieh HS et al.. (2016) Discovery of N-(4-Fluoro-3-methoxybenzyl)-6-(2-(((2S,5R)-5-(hydroxymethyl)-1,4-dioxan-2-yl)methyl)-2H-tetrazol-5-yl)-2-methylpyrimidine-4-carboxamide. A Highly Selective and Orally Bioavailable Matrix Metalloproteinase-13 Inhibitor for the Potential Treatment of Osteoarthritis. J Med Chem, 59 (1): 313-27. [PMID:26653735]

11. 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]

12. Taylor SJ, Abeywardane A, Liang S, Muegge I, Padyana AK, Xiong Z, Hill-Drzewi M, Farmer B, Li X, Collins B et al.. (2011) Fragment-based discovery of indole inhibitors of matrix metalloproteinase-13. J Med Chem, 54 (23): 8174-87. [PMID:22017539]

13. Troeberg L, Nagase H. (2012) Proteases involved in cartilage matrix degradation in osteoarthritis. Biochim Biophys Acta, 1824 (1): 133-45. [PMID:21777704]

14. Vizoso FJ, González LO, Corte MD, Corte MG, Bongera M, Martínez A, Martín A, Andicoechea A, Gava RR. (2006) Collagenase-3 (MMP-13) expression by inflamed mucosa in inflammatory bowel disease. Scand J Gastroenterol, 41 (9): 1050-5. [PMID:16938718]

15. Xue CB, Voss ME, Nelson DJ, Duan JJ, Cherney RJ, Jacobson IC, He X, Roderick J, Chen L, Corbett RL et al.. (2001) Design, synthesis, and structure-activity relationships of macrocyclic hydroxamic acids that inhibit tumor necrosis factor alpha release in vitro and in vivo. J Med Chem, 44 (16): 2636-60. [PMID:11472217]

16. Yoshihara Y, Nakamura H, Obata K, Yamada H, Hayakawa T, Fujikawa K, Okada Y. (2000) Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis, 59 (6): 455-61. [PMID:10834863]

How to cite this page

M10: Matrix metallopeptidase: MMP13. Last modified on 10/05/2023. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1637.