MMP9

Target id: 1633

Nomenclature: MMP9

Family: M10: Matrix metallopeptidase

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     MMP9 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 707 20q12-q13 MMP9 matrix metallopeptidase 9
Mouse - 730 2 H1-H2 Mmp9 matrix metallopeptidase 9
Rat - 708 3q42 Mmp9 matrix metallopeptidase 9
Previous and Unofficial Names
GELB | gelatinase B | B/MMP9 | CLG4B | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)
Database Links
Specialist databases
MEROPS M10.004 (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
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.4.24.35

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
compound 1a [PMID: 15055993] Hs Inhibition 10.2 pKi 11
pKi 10.2 (Ki 6x10-11 M) [11]
SL422 Hs Inhibition 9.1 pKi 14
pKi 9.1 (Ki 9x10-10 M) [14]
compound 29e [PMID: 23631440] Hs Inhibition 8.8 pKi 6
pKi 8.8 (Ki 1.5x10-9 M) [6]
SB-3CT Hs Inhibition 6.2 pKi 4
pKi 6.2 (Ki 6x10-7 M) [4]
AZD6605 Hs Inhibition 8.7 pIC50 12
pIC50 8.7 (IC50 2x10-9 M) [12]
AZD1236 Hs Inhibition 8.4 pIC50 2
pIC50 8.4 (IC50 4.5x10-9 M) [2]
CGS-27023A Hs Inhibition 8.3 pIC50 13
pIC50 8.3 (IC50 4.8x10-9 M) [13]
ilomastat Hs Inhibition 7.8 pIC50 9
pIC50 7.8 (IC50 1.5x10-8 M) [9]
Inhibitor Comments
SL422 is a broad-spectrum inhibitor of MMP enzymes [14].
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Affinity Units Reference
andecaliximab Hs Binding 9.7 pIC50 10
pIC50 9.7 (IC50 2.18x10-10 M) [10]
Immunopharmacology Comments
Mucosal up-regulation of MMP-9 correlates with the severity of inflammation in ulcerative colitis, and may be responsible for the mucosal damage in active ulcerative colitis [8].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process ID:  2
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  neutrophil degranulation (GO:0043312) TAS
leukocyte migration (GO:0050900) IEA
References: 
Immuno Process:  Immune system development
Immuno Process ID:  8
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  macrophage differentiation (GO:0030225) TAS
References: 
Immuno Process:  Cellular signalling
Immuno Process ID:  11
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  neutrophil degranulation (GO:0043312) TAS
References: 
Immuno Process:  Chemotaxis & migration
Immuno Process ID:  10
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  leukocyte migration (GO:0050900) IEA
References: 
Immuno Disease Associations
Disease Name:  Multiple Sclerosis
Disease Synonyms:  no synonynms
Comment:  MMP9 is upregulated in cerebrospinal fluid (CSF), blood and brain tissue of MS patients, can be a useful biomarker and expression level is reduced in response to MS treatment with interferon beta.
Disease X-refs:  Disease Ontology: DOID:2377
OMIM: 126200
Orphanet: ORPHA802
References:  1,3,15
Disease Name:  Irritable bowel syndrome
Disease Synonyms:  no synonynms
Comment:  MMP9 is suggested to be implicated in fistula formation in IBD. Upregulated mucosal MMP9 expression correlates with disease severity. MMP9 selective inhibitors are in development for the treatment of IBD.
Disease X-refs:  Disease Ontology: DOID:9778
References:  7-8,10
Disease Name:  Asthma
Disease Synonyms:  no synonynms
Comment:  MMP2 and MMP9 can promote the egress of inflammatory cells into airway lumen, suggesting a protective anti-inflammatory role in asthma. MMP2/MMP9 gelatinolytic activity is elevated in the sputum of asthmatic patients.
Disease X-refs:  Disease Ontology: DOID:2841
OMIM: 600807
References:  5
Clinically-Relevant Mutations and Pathophysiology
Disease:  Intervertebral disc disease; IDD
Disease Ontology: DOID:9321
OMIM: 603932
Disease:  Metaphyseal anadysplasia 2; MANDP2
Synonyms: Metaphyseal anadysplasia [Orphanet: ORPHA1040]
OMIM: 613073
Orphanet: ORPHA1040

References

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1. Anthony DC, Ferguson B, Matyzak MK, Miller KM, Esiri MM, Perry VH. (1997) Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke. Neuropathol Appl Neurobiol.23 (5): 406-15. [PMID:9364466]

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

3. Benesová Y, Vasku A, Novotná H, Litzman J, Stourac P, Beránek M, Kadanka Z, Bednarík J. (2009) Matrix metalloproteinase-9 and matrix metalloproteinase-2 as biomarkers of various courses in multiple sclerosis. Mult Scler.15 (3): 316-22. [PMID:19153173]

4. Brown S, Bernardo MM, Li Z-H, Kotra LP, Tanaka Y, Fridman R, Mobashery S. (2000) Potent and Selective Mechanism-Based Inhibition of Gelatinases. J. Am. Chem. Soc.122: 6799-6800.

5. Cataldo D, Munaut C, Noël A, Frankenne F, Bartsch P, Foidart JM, Louis R. (2000) MMP-2- and MMP-9-linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease. Int. Arch. Allergy Immunol.123 (3): 259-67. [PMID:11112863]

6. 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]

7. Kirkegaard T, Hansen A, Bruun E, Brynskov J. (2004) Expression and localisation of matrix metalloproteinases and their natural inhibitors in fistulae of patients with Crohn's disease. Gut53 (5): 701-9. [PMID:15082589]

8. Lakatos G, Sipos F, Miheller P, Hritz I, Varga MZ, Juhász M, Molnár B, Tulassay Z, Herszényi L. (2012) The behavior of matrix metalloproteinase-9 in lymphocytic colitis, collagenous colitis and ulcerative colitis. Pathol. Oncol. Res.18 (1): 85-91. [PMID:21678108]

9. 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]

10. Marshall DC, Lyman SK, McCauley S, Kovalenko M, Spangler R, Liu C, Lee M, O'Sullivan C, Barry-Hamilton V, Ghermazien H et al.. (2015) Selective Allosteric Inhibition of MMP9 Is Efficacious in Preclinical Models of Ulcerative Colitis and Colorectal Cancer. PLoS ONE10 (5): e0127063. [PMID:25961845]

11. Moriyama H, Tsukida T, Inoue Y, Yokota K, Yoshino K, Kondo H, Miura N, Nishimura S. (2004) Azasugar-based MMP/ADAM inhibitors as antipsoriatic agents. J. Med. Chem.47 (8): 1930-8. [PMID:15055993]

12. 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

13. 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 Chem46 (7): 2617-29. [PMID:21514700]

14. 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]

15. Yong VW, Zabad RK, Agrawal S, Goncalves Dasilva A, Metz LM. (2007) Elevation of matrix metalloproteinases (MMPs) in multiple sclerosis and impact of immunomodulators. J Neurol Sci.259: 79-84. [PMID:17382965]

How to cite this page

M10: Matrix metallopeptidase: MMP9. Last modified on 16/03/2017. Accessed on 20/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1633.