Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix metalloproteinases (MMPs, matrixins) are a family of homologous zinc endopeptidases that may play a very important role in many physiological and pathological processes, e.g., the initiation of angiogenesis. Two new matrixin inhibitors were synthesized and characterized. A thiol inhibitor MAG-283 had IC(50) values of 480, 3, 280, 14, 1.1, and 2.3 nM against human interstitial collagenase (MMP-1), gelatinase A (MMP-2), stromelysin (MMP-3), matrilysin (MMP-7), neutrophil collagenase (MMP-8), and gelatinase B (MMP-9), respectively. A sulfodiimine inhibitor YLL-224 had IC(50) values of 180, 63, 4500, 210, 5.9, and 44 nM against MMP-1, -2, -3, -7, -8, and -9, respectively. Human skin microvascular endothelial cells were treated with these two compounds in culture. These inhibitors at very low micromolar concentrations suppressed proliferation of the endothelial cells stimulated by acidic fibroblast growth factor and vascular endothelial growth factor. They also partially blocked cell invasion through type IV collagen. These results suggested a correlation between the anti-metalloenzyme activity and the effects of these inhibitors on the growth and invasion of endothelial cells.
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PMID:New thiol and sulfodiimine metalloproteinase inhibitors and their effect on human microvascular endothelial cell growth. 1092 54

Matrix metalloproteinases (MMPs, matrixins) are a family of zinc proteinases that digest extracellular matrix and play a very important role in normal development and pathological conditions such as cardiovascular diseases and cancer metastasis. Type IV collagenases (gelatinase A/MMP-2 and gelatinase B/MMP-9) may be critical in the early steps of angiogenesis, the digestion of basement membrane and the migration of endothelial cells from the existing blood vessels. Human dermal microvascular endothelial cells were cultured on type I collagen, type IV collagen, and reconstituted basement membrane Matrigel and differentiation was examined in the presence of potent synthetic inhibitors of MMPs. The thiol inhibitor MAG-283 had IC50 values of 480 nM and 3 nM against human interstitial collagenase (MMP-1) and MMP-2, respectively, and KI value of 2.2 nM against MMP-9. The sulfodiimine inhibitor YLL-224 had IC50 values of 180 nM, 63 nM, and 44 nM against MMP-1, -2, and -9, respectively. These inhibitors at very low micromolar concentrations inhibited cell-mediated type I collagen degradation and partially blocked cell invasion through type IV collagen. These inhibitors also suppressed endothelial differentiation, i.e., formation of capillary-like tubes on Matrigel and on type I collagen. These results suggest that collagen-degrading MMPs play an important role during the initiation of angiogenesis.
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PMID:Suppression of human microvascular endothelial cell invasion and morphogenesis with synthetic matrixin inhibitors. Targeting angiogenesis with MMP inhibitors. 1094 65