The Design, Structure, and Therapeutic Application of Matrix Metalloproteinase Inhibitors
Authors: Skiles, J.W.; Gonnella, N.C.; Jeng, A.Y.
Source: Current Medicinal Chemistry, Volume 8, Number 4, March 2001 , pp. 425-474(50)
Publisher: Bentham Science Publishers
Abstract:Matrix metalloproteinases (MMPs) are a family of zinc-containing enzymes involved in the degradation and remodeling of extracellular matrix proteins. The activities of these enzymes are well regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). Chronic stimulation of MMP activities due to an imbalance in the levels of MMPs and TIMPs has been implicated in the pathogenesis of a variety of diseases such as cancer, osteoarthritis, and rheumatoid arthritis. Thus, MMP inhibitors are expected to be useful for the treatment of these disorders. This article reviews briefly the biochemistry of MMPs and evidence for their pathogenic roles using molecular biology approaches. Biomolecular structures used in the design of MMP inhibitors are thoroughly covered. Major emphasis is on recently published potent, small molecular weight MMP inhibitors and their pharmacological properties. Finally, available clinical results of compounds in development are summarized.
Keywords: Biaryl oxime; Metalloproteinase inhibitors; angiogenesis; gelatinase; hydroxamate moiety; murine model; non peptidic sulfonamide; spiro cyclopentyl; tumor induced; uninhibited catalytic domain
Document Type: Review Article
Publication date: March 1, 2001
- Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.