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MMP9

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1633

Nomenclature: MMP9

Family: M10: Matrix metallopeptidase

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 707 20q13.12 MMP9 matrix metallopeptidase 9
Mouse - 730 2 85.27 cM Mmp9 matrix metallopeptidase 9
Rat - 708 3q42 Mmp9 matrix metallopeptidase 9
Previous and Unofficial Names Click here for help
GELB | gelatinase B | B/MMP9 | CLG4B | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)
Database Links Click here for help
Specialist databases
MEROPS M10.004 (Hs)
Other databases
Alphafold P14780 (Hs), P41245 (Mm), P50282 (Rn)
BRENDA 3.4.24.35
CATH/Gene3D 1.10.101.10, 2.10.10.10, 2.110.10.10, 3.40.390.10
ChEMBL Target CHEMBL321 (Hs), CHEMBL2214 (Mm), CHEMBL3870 (Rn)
DrugBank Target P14780 (Hs)
Ensembl Gene ENSG00000100985 (Hs), ENSMUSG00000017737 (Mm), ENSRNOG00000017539 (Rn)
Entrez Gene 4318 (Hs), 17395 (Mm), 81687 (Rn)
Human Protein Atlas ENSG00000100985 (Hs)
KEGG Enzyme 3.4.24.35
KEGG Gene hsa:4318 (Hs), mmu:17395 (Mm), rno:81687 (Rn)
OMIM 120361 (Hs)
Orphanet ORPHA208342 (Hs)
Pharos P14780 (Hs)
RefSeq Nucleotide NM_004994 (Hs), NM_013599 (Mm), NM_031055 (Rn)
RefSeq Protein NP_004985 (Hs), NP_038627 (Mm), NP_112317 (Rn)
UniProtKB P14780 (Hs), P41245 (Mm), P50282 (Rn)
Wikipedia MMP9 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure determination of a potent, selective antibody inhibitor of human MMP9 (GS-5745 bound to MMP-9).
PDB Id:  5TH9
Ligand:  andecaliximab
Resolution:  2.99Å
Species:  Human
References:  2
Enzyme Reaction Click here for help
EC Number: 3.4.24.35

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
compound 1a [PMID: 15055993] Small molecule or natural product Primary target of this compound Hs Inhibition 10.2 pKi 12
⤷ pKi 10.2 (Ki 6x10-11 M) [12]
SL422 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.1 pKi 18
⤷ pKi 9.1 (Ki 9x10-10 M) [18]
compound 29e [PMID: 23631440] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.8 pKi 7
⤷ pKi 8.8 (Ki 1.5x10-9 M) [7]
(R)-ND-336 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pKi 14
⤷ pKi 7.7 (Ki 1.9x10-8 M) [14]
SB-3CT Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pKi 5
⤷ pKi 6.2 (Ki 6x10-7 M) [5]
AZD6605 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.7 pIC50 13
⤷ pIC50 8.7 (IC50 2x10-9 M) [13]
marimastat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pIC50 16
⤷ pIC50 8.5 (IC50 3x10-9 M) [16]
ilomastat Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 – 9.0 pIC50 10,17
⤷ pIC50 9.0 (IC50 9.3x10-10 M) [17]
pIC50 7.8 (IC50 1.5x10-8 M) [10]
AZD1236 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.4 pIC50 3
⤷ pIC50 8.4 (IC50 4.5x10-9 M) [3]
CGS-27023A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.3 pIC50 15
⤷ pIC50 8.3 (IC50 4.8x10-9 M) [15]
TP0556351 Peptide Click here for species-specific activity table Hs Inhibition 5.1 pIC50 17
⤷ pIC50 5.1 (IC50 8.508x10-6 M) [17]
Inhibitor Comments
SL422 is a broad-spectrum inhibitor of MMP enzymes [18].
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
andecaliximab Peptide Primary target of this compound Immunopharmacology Ligand Hs Binding 9.7 pIC50 11
⤷ pIC50 9.7 (IC50 2.18x10-10 M) [11]
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 [9].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
Immuno Process:  Immune regulation
Immuno Process:  Chemotaxis & migration
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:  1,4,19
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:  8-9,11
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:  6
Clinically-Relevant Mutations and Pathophysiology Click here for help
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. Appleby TC, Greenstein AE, Hung M, Liclican A, Velasquez M, Villaseñor AG, Wang R, Wong MH, Liu X, Papalia GA et al.. (2017) Biochemical characterization and structure determination of a potent, selective antibody inhibitor of human MMP9. J Biol Chem, 292 (16): 6810-6820. [PMID:28235803]

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

4. 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]

5. 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.

6. 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]

7. 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]

8. 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. Gut, 53 (5): 701-9. [PMID:15082589]

9. 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]

10. 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]

11. 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 ONE, 10 (5): e0127063. [PMID:25961845]

12. 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]

13. 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

14. Nguyen TT, Ding D, Wolter WR, Pérez RL, Champion MM, Mahasenan KV, Hesek D, Lee M, Schroeder VA, Jones JI et al.. (2018) Validation of Matrix Metalloproteinase-9 (MMP-9) as a Novel Target for Treatment of Diabetic Foot Ulcers in Humans and Discovery of a Potent and Selective Small-Molecule MMP-9 Inhibitor That Accelerates Healing. J Med Chem, 61 (19): 8825-8837. [PMID:30212201]

15. 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 Chem, 46 (7): 2617-29. [PMID:21514700]

16. Rasmussen HS, McCann PP. (1997) Matrix metalloproteinase inhibition as a novel anticancer strategy: a review with special focus on batimastat and marimastat. Pharmacol Ther, 75 (1): 69-75. [PMID:9364582]

17. 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]

18. 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]

19. 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 12/07/2022. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1633.