Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases.
Matrix metalloproteinases (MMPs) have outgrown the field of extracellular-matrix biology and have progressed towards being important regulatory molecules in cancer and inflammation. This rise in status was accompanied by the development of various classes of inhibitors. Although clinical trials with synthetic inhibitors for the treatment of cancer were disappointing, recent data indicate that the use of selective inhibitors might lead to new therapies for acute and chronic inflammatory and vascular diseases. In this Review, we compare the major classes of MMP inhibitors and advocate that future drug discovery should be based on crucial insights into the differential roles of specific MMPs in pathophysiology obtained with animal models, including knockout studies.
Hu
Jialiang
J
Rega Institute for Medical Research, Catholic University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Van den Steen
Philippe E
PE
Sang
Qing-Xiang A
QX
Opdenakker
Ghislain
G
D000818:Animals; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000502:physiology; D009369:Neoplasms / Q000276:immunology; D009928:Organ Specificity; D010195:Pancreatitis / Q000188:drug therapy; D011480:Protease Inhibitors / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D011658:Pulmonary Fibrosis / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014652:Vascular Diseases / Q000188:drug therapy*
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases