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
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
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0060339 negative regulation of type I interferon-mediated signaling pathway IEA
GO:0060340 positive regulation of type I interferon-mediated signaling pathway IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 3 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0050691 regulation of defense response to virus by host IEA
GO:0060339 negative regulation of type I interferon-mediated signaling pathway IEA
GO:0060340 positive regulation of type I interferon-mediated signaling pathway IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 3 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0060339 negative regulation of type I interferon-mediated signaling pathway IEA
GO:0060340 positive regulation of type I interferon-mediated signaling pathway IEA
GO:1902741 positive regulation of interferon-alpha secretion IEA
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. 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 21/07/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1636.