MMP12

Target id: 1636

Nomenclature: MMP12

Family: M10: Matrix metallopeptidase

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     MMP12 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 470 11q22.3 MMP12 matrix metallopeptidase 12
Mouse - 473 9 A1 Mmp12 matrix metallopeptidase 12
Rat - 477 8q11 Mmp12 matrix metallopeptidase 12
Previous and Unofficial Names
Mme | Mmel | Macrophage metalloelastase | matrix metallopeptidase 12 (macrophage elastase)
Database Links
Specialist databases
MEROPS M10.009 (Hs)
Other databases
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.4.24.65

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
RXP470.1 Hs Inhibition 8.6 pKi 3
pKi 8.6 (Ki 2.4x10-9 M) [3]
compound 20 [PMID: 22153340] Hs Inhibition 10.0 pIC50 7
pIC50 10.0 (IC50 1x10-10 M) [7]
AZD6605 Hs Inhibition 9.2 pIC50 5
pIC50 9.2 (IC50 6x10-10 M) [5]
AZD1236 Hs Inhibition 8.2 pIC50 1
pIC50 8.2 (IC50 6.1x10-9 M) [1]
ilomastat Hs Inhibition 7.9 pIC50 4
pIC50 7.9 (IC50 1.3x10-8 M) [4]
compound 1 [PMID: 24900526] Hs Inhibition 6.5 pIC50 2
pIC50 6.5 (IC50 2.9x10-7 M) [2]
compound 5 [PMID: 24900526] 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 ID:  2
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  negative regulation of type I interferon-mediated signaling pathway (GO:0060339) IEA
positive regulation of type I interferon-mediated signaling pathway (GO:0060340) IEA
References: 
Immuno Process:  Immune regulation
Immuno Process ID:  6
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  regulation of defense response to virus by host (GO:0050691) IEA
negative regulation of type I interferon-mediated signaling pathway (GO:0060339) IEA
positive regulation of type I interferon-mediated signaling pathway (GO:0060340) IEA
References: 
Immuno Process:  Cytokine production & signalling
Immuno Process ID:  9
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  negative regulation of type I interferon-mediated signaling pathway (GO:0060339) IEA
positive regulation of type I interferon-mediated signaling pathway (GO:0060340) IEA
positive regulation of interferon-alpha secretion (GO:1902741) IEA
References: 
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 Lett3 (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. 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 19/04/2017. Accessed on 15/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1636.