Pharmacomodulation of Broad Spectrum Matrix Metalloproteinase Inhibitors Towards Regulation of Gelatinases
نویسندگان
چکیده
منابع مشابه
Matrix metalloproteinases and processing of pro-TNF-alpha.
Tumor necrosis factor-alpha (TNF-alpha) is released from a cell membrane-anchored precursor by proteolytic cleavage. We have shown that broad spectrum synthetic inhibitors of matrix metalloproteinases (MMPs) prevent the processing of the TNF precursor but do not inhibit the release of other cytokines. Purified MMPs, stromelysin, matrilysin, collagenase, and the gelatinases can all cleave a reco...
متن کاملSecretion of matrix metalloproteinase-2, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases into the intrauterine compartments during early pregnancy.
Matrix metalloproteinases (MMPs) are important enzymes in tissue remodelling, a key event for the development of the fetal membranes and placenta and establishing the feto-maternal interface during early pregnancy. This study has examined the secretion of the gelatinases, MMP-2 (72 kDa) and MMP-9 (92 kDa), and the endogenous tissue inhibitors of metalloproteinases (TIMPs) into extra-embryonic c...
متن کاملIncrease in gelatinase-specificity of matrix metalloproteinase inhibitors correlates with antimetastatic efficacy in a T-cell lymphoma model.
The recognition that matrix metalloproteinases (MMPs) facilitate tumor cell invasion and metastasis has led to the development of synthetic MMP inhibitors (MMPIs) as cancer therapeutic agents. Because several Phase III trials failed recently to show efficacy of broad-spectrum MMPIs in advanced cancer, the feasibility of MMPs as therapeutic targets has been challenged. However, it has not yet be...
متن کاملInhibition of MMP synthesis by doxycycline and chemically modified tetracyclines (CMTs) in human endothelial cells.
Doxycycline is a commonly used broad-spectrum antibiotic. Recently, it has been shown that it also inhibits the activity of mammalian collagenases and gelatinases, an activity unrelated to its antimicrobial efficacy. In this study, we show that doxycycline not only inhibits MMP-8 and MMP-9 (gelatinase B) activity, but also the synthesis of MMPs in human endothelial cells. Doxycycline (50 microM...
متن کاملA peptide hydroxamate library for enrichment of metalloproteinases: towards an affinity-based metalloproteinase profiling protocol.
A compound library of 96 enantiopure N-terminal succinyl hydroxamate functionalized peptides was synthesized on solid phase. All compounds were tested for their inhibitory potential towards MMP-9, MMP-12 and ADAM-17, which led to the identification of both broad spectrum inhibitors and metalloproteinase-selective ones. Eight potent and less potent inhibitors were immobilized on Sepharose beads ...
متن کامل