MMP-9

Synonyms

EC:3.4.24.35, EC 3.4.24, CLG4B, MMP9, Matrix Metallopeptidase 9, Matrix Metalloproteinase 9 (Gelatinase B, 92kDa Gelatinase, 92kDa Type IV Collagenase), GELB, Matrix Metalloproteinase-9, 92 KDa Type IV Collagenase, Macrophage Gelatinase, Type V Collagenase, Gelatinase B, EC 3.4.24.35, MANDP2, Matrix Metalloproteinase 9, 92 kDa gelatinase, MMP-9, Matrix Metallopeptidase 9 (Gelatinase B, 92kDa Gelatinase, 92kDa Type IV Collagenase)

Description

Matrix metallopeptidase 9 (MMP-9), also known as 92 kDa type IV collagenase, 92 kDa gelatinase or gelatinase B (GELB), is a matrixin, a class of enzymes that belong to the zinc-metalloproteinases family involved in the degradation of the extracellular matrix. In humans the MMP9 gene encodes for a signal peptide, a propeptide, a catalytic domain with inserted three repeats of fibronectin type II domain followed by a C-terminal hemopexin-like domain. It plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.

KO Status

RenMab: Immunization

Drug Information

Launched drug: 1
Drugs in clinical trials: 3
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Andecaliximab

GS-5745

Phase 2 Clinical

Gilead

Cystic Fibrosis, Stomach Neoplasms, Esophageal Neoplasms, Pancreatic Neoplasms, Arthritis, Rheumatoid, Breast Neoplasms, Colorectal Neoplasms, Colitis, Ulcerative, Pulmonary Disease, Chronic Obstructive, Carcinoma, Non-Small-Cell Lung, Crohn Disease, Adenocarcinoma

DP-b99

DP-b99, DP-Bapta-99

Phase 2 Clinical

D-Pharm

Brain Ischemia, Pancreatitis, Cerebrovascular Disorders, Stroke

AQU-005

AQU-005, NMAQU-005, NM-AQU-005

Phase 1 Clinical

Aquilus Pharmaceuticals

Neuralgia

CALY-001

CALY-001

Clinical

Calypso Biotech

Inflammatory Bowel Diseases, Crohn Disease

S-3304

S-3304

Pending

Shionogi & Co Ltd

Solid tumours, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

Incyclinide

CMT-3, COL-3, NSC-683551

Discontinued

Galderma

Acne Vulgaris, Rosacea

SD-7300

Discontinued

Pfizer Pharmaceuticals Ltd (China)

Neoplasms

ABT-518

ABT 518

Discontinued

Abbvie Inc

Neoplasms

RS-130830

CTS-1027, RS-130830, RO-1130830

Discontinued

F. Hoffmann-La Roche Ltd

Hepatitis C, Arthritis, Hepatitis C, Chronic

CP-471358

CP-471358

Discontinued

Pfizer Pharmaceuticals Ltd (China)

Neoplasms

References


Title

Authors

Source

Structure of the C-terminally truncated human ProMMP9, a gelatin-binding matrix metalloproteinase

Elkins P.A., Ho Y.S., Smith W.W., Janson C.A., D'Alessio K.J., McQueney M.S., Cummings M.D., Romanic A.M.,

Acta Crystallogr. D 58:1182-1192(2002)

Crystal structure of human MMP9 in complex with a reverse hydroxamate inhibitor

Rowsell S., Hawtin P., Minshull C.A., Jepson H., Brockbank S.M.V., Barratt D.G., Slater A.M., McPheat W.L., Waterson D., Henney A.M., Pauptit R.A.,

J. Mol. Biol. 319:173-181(2002)

The DNA sequence and comparative analysis of human chromosome 20

Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E., Rogers J.,

Nature 414:865-871(2001)

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)

The MGC Project Team,

Genome Res. 14:2121-2127(2004)

Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells

Sato H., Seiki M.,

Oncogene 8:395-405(1993)

Human neutrophil gelatinase: a marker for circulating blood neutrophils. Purification and quantitation by enzyme linked immunosorbent assay

Kjeldsen L., Bjerrum O.W., Hovgaard D., Johnsen A.H., Sehested M., Borregaard N.,

Eur. J. Haematol. 49:180-191(1992)

The cytokine-protease connection: identification of a 96-kD THP-1 gelatinase and regulation by interleukin-1 and cytokine inducers

van Ranst M., Norga K., Masure S., Proost P., Vandekerckhove F., Auwerx J., van Damme J., Opdenakker G.,

Cytokine 3:231-239(1991)

Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9

Ogata Y., Enghild J.J., Nagase H.,

J. Biol. Chem. 267:3581-3584(1992)

Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties

Okada Y., Gonoji Y., Naka K., Tomita K., Nakanishi I., Iwata K., Yamashita K., Hayakawa T.,

J. Biol. Chem. 267:21712-21719(1992)

Proteolytic and non-proteolytic activation of human neutrophil progelatinase B

Sang Q.X., Birkedal-Hansen H., Van Wart H.E.,

Biochim. Biophys. Acta 1251:99-108(1995)