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MMP12

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1636

Nomenclature: MMP12

Family: M10: Matrix metallopeptidase

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 470 11q22.2 MMP12 matrix metallopeptidase 12
Mouse - 473 9 2.46 cM Mmp12 matrix metallopeptidase 12
Rat - 465 8q11 Mmp12 matrix metallopeptidase 12
Previous and Unofficial Names Click here for help
Mme | Mmel | Macrophage metalloelastase | matrix metallopeptidase 12 (macrophage elastase)
Database Links Click here for help
Specialist databases
MEROPS M10.009 (Hs)
Other databases
Alphafold P39900 (Hs), P34960 (Mm), Q63341 (Rn)
BRENDA 3.4.24.65
CATH/Gene3D 3.40.390.10, 2.110.10.10
ChEMBL Target CHEMBL4393 (Hs), CHEMBL2594 (Mm), CHEMBL5506 (Rn)
DrugBank Target P39900 (Hs)
Ensembl Gene ENSG00000262406 (Hs), ENSMUSG00000049723 (Mm), ENSRNOG00000030187 (Rn)
Entrez Gene 4321 (Hs), 17381 (Mm), 117033 (Rn)
Human Protein Atlas ENSG00000262406 (Hs)
KEGG Enzyme 3.4.24.65
KEGG Gene hsa:4321 (Hs), mmu:17381 (Mm), rno:117033 (Rn)
OMIM 601046 (Hs)
Pharos P39900 (Hs)
RefSeq Nucleotide NM_002426 (Hs), NM_008605 (Mm), NM_053963 (Rn)
RefSeq Protein NP_002417 (Hs), NP_032631 (Mm), NP_446415 (Rn)
SynPHARM 80658 (in complex with RXP470.1)
UniProtKB P39900 (Hs), P34960 (Mm), Q63341 (Rn)
Wikipedia MMP12 (Hs)
Enzyme Reaction Click here for help
EC Number: 3.4.24.65

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
RXP470.1 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.6 pKi 3
⤷ pKi 8.6 (Ki 2.4x10-9 M) [3]
compound 20 [PMID: 22153340] Small molecule or natural product Hs Inhibition 10.0 pIC50 8
⤷ pIC50 10.0 (IC50 1x10-10 M) [8]
AZD6605 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 9.2 pIC50 5
⤷ pIC50 9.2 (IC50 6x10-10 M) [5]
ilomastat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.9 – 9.3 pIC50 4,7
⤷ pIC50 9.3 (IC50 4.6x10-10 M) [7]
pIC50 7.9 (IC50 1.3x10-8 M) [4]
AZD1236 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.2 pIC50 1
⤷ pIC50 8.2 (IC50 6.1x10-9 M) [1]
compound 1 [PMID: 24900526] Small molecule or natural product Primary target of this compound Hs Inhibition 6.5 pIC50 2
⤷ pIC50 6.5 (IC50 2.9x10-7 M) [2]
TP0556351 Peptide Click here for species-specific activity table Hs Inhibition 5.9 pIC50 7
⤷ pIC50 5.9 (IC50 1.367x10-6 M) [7]
compound 5 [PMID: 24900526] Small molecule or natural product Hs Inhibition 4.9 pIC50 2
⤷ pIC50 4.9 (IC50 1.3x10-5 M) This is the prodrug [2]
Immunopharmacology Comments
MMP12 is included in GtoImmuPdb based on its reported involvement in asthma and potential as a asthma therapeutic target.
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Immuno Disease Associations
Disease Name:  Asthma
Disease Synonyms:  no synonynms
Comment:  a common serine variant of the MMP12 gene in human (rs652438) causes more aggressive extracellular matrix degradation and is positively associated with disease severity. Thus MMP12 is a drug target for novel asthma therapeutics.
Disease X-refs:  Disease Ontology: DOID:2841
OMIM: 600807
References:  6

References

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1. AstraZeneca. AZD1236. Accessed on 31/10/2014. Modified on 31/10/2014. Open Innovation, http://openinnovation.astrazeneca.com/what-we-offer/compound/azd1236/

2. Cobos-Correa A, Stein F, Schultz C. (2012) Target-Activated Prodrugs (TAPs) for the Autoregulated Inhibition of MMP12. ACS Med Chem Lett, 3 (8): 653-7. [PMID:24900526]

3. Czarny B, Stura EA, Devel L, Vera L, Cassar-Lajeunesse E, Beau F, Calderone V, Fragai M, Luchinat C, Dive V. (2013) Molecular determinants of a selective matrix metalloprotease-12 inhibitor: insights from crystallography and thermodynamic studies. J Med Chem, 56 (3): 1149-59. [PMID:23343195]

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. Mukhopadhyay S, Sypek J, Tavendale R, Gartner U, Winter J, Li W, Page K, Fleming M, Brady J, O'Toole M et al.. (2010) Matrix metalloproteinase-12 is a therapeutic target for asthma in children and young adults. J Allergy Clin Immunol, 126 (1): 70-6.e16. [PMID:20546881]

7. 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]

8. Wu Y, Li J, Wu J, Morgan P, Xu X, Rancati F, Vallese S, Raveglia L, Hotchandani R, Fuller N et al.. (2012) Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD). Bioorg Med Chem Lett, 22 (1): 138-43. [PMID:22153340]

How to cite this page

M10: Matrix metallopeptidase: MMP12. Last modified on 12/07/2022. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1636.