Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Novel endothelin converting enzyme (ECE) inhibitors, WS75624 A and B, have been isolated from the fermentation broth of Saccharothrix sp. No. 75624. These inhibitors were purified from an acetone extract of whole culture broth followed by HP-20 column chromatography, silica gel column chromatography and HPLC. WS75624 A and B showed highly potent ECE inhibitory activity, and both had IC50 values of 0.03 microgram/ml. WS75624 A and B also showed other metalloprotease (collagenase and neutral endopeptidase) inhibitory activity with IC50 values of 1 microgram/ml. Since large amount of WS75624 B was isolated, we tried in vivo evaluation using WS75624 B. WS75624 B inhibited big endothelin-induced pressor effect when administered to SD rat intravenously with big ET-1.
 ...
PMID:WS75624 A and B, new endothelin converting enzyme inhibitors isolated from Saccharothrix sp. No. 75624. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities. 749 Feb 8

An animal model of liver metastasis was established by injection of suspending tumor cells into subcapsule of spleen in nude mice. With additional mechanic disaggregation, single-tumor cell suspension was prepared by enzymatic disaggregation, including trypsin-collagenase disaggregate medium treatment, from the subcutaneous MGC 80-3 xeno-transplanted tumor and filtered through filter holders with different pore size. To investigate the effect of liver damage by carbon tetrachloride (CCL4) on the metastatic potential of MGC 80-3 cells injected intrasplenically, the nude mice were divided into 2 groups: Group 1 received intrasplenic injection of 1.25 x 10(6) MGC 80-3 cells without CCL4 treatment; Group 2 received intrasplenic injection of equal cells with CCL4 treatment. The incidence of liver metastasis was 60% in Group 1, but 100% in Group 2. The mean numbers of metastatic nodules per liver were 1.80 in Group 1, but 4.85 in Group 2. It is obvious that the incidence and nodules of liver metastasis were increased in the mice treated with CCL4. This is a useful model to study antimetastatic agents and metastatic behaviors.
 ...
PMID:[Establishment of a model of human gastric cancer with liver metastasis in nude mice]. 826 64

PD 069185 is a highly selective and structurally novel inhibitor of endothelin converting enzyme-1 (ECE-1). PD 069185 is a trisubstituted quinazoline with an IC50 value of 0.9 +/- 0.1 microns for inhibition of human ECE-1 from the solubilized membrane fraction of CHO cells stably transfected with human ECE-1 cDNA. Kinetic analysis revealed that PD 069185 is best fit with a competitive inhibition model with a Ki value of 1.1 +/- 0.1 microns and binds in a reversible manner. The closely related enzyme, ECE-2, is not inhibited at up to 100 microns PD 069185. In addition, PD 069185 at 200-300 microns has little effect on other metalloproteases, such as neutral endopeptidase 24.11, stromelysin, gelatinase A, and collagenase, showing a high ECE-1 specificity. Data are also presented to show that this series of inhibitors are effective in inhibiting ECE-1 in intact cells and in attenuating the increase in perfusion pressure induced by big ET-1 in isolated rat mesentery. These non-peptidic ECE-1 inhibitors should serve as a valuable tool to study the pathophysiological role of endothelin and the therapeutic potential of ECE-1 inhibitors.
 ...
PMID:Novel selective quinazoline inhibitors of endothelin converting enzyme-1. 947 2

Premature delivery occurs in 12% of all births, accounts for nearly half of neonatal morbidity and is increasing in frequency. Current therapeutic approaches to preterm delivery are ineffective and present serious risks to both the mother and fetus. Although there are multiple factors that contribute to the etiology of preterm birth, the single most common cause is infection. Recently, using cDNA microarray analysis of human placental tissue, we demonstrated that human placental matrix metalloproteinase-1 (MMP-1) is upregulated during labor. In a separate line of investigation, we have shown that blockade of endothelin-1 (ET-1) action through the use of an endothelin-converting enzyme-1 (ECE-1) inhibitor, an established commercially available endothelin receptor antagonist or a novel quinolone-derived endothelin receptor antagonist synthesized by our group also prevents preterm labor and delivery in a mouse model. We have now shown that induction of preterm labor with lipopolysaccharide in our mouse model is associated with increased levels of MMP-1. Furthermore, we showed that silencing the ECE-1/ET-1 pathway by using ECE-1 RNA interference prevents both the onset of preterm labor and upregulation of MMP-1. The data indicate that ET-1 and MMP-1 act in the same molecular pathway in preterm labor.
 ...
PMID:Prevention of inflammation-associated preterm birth by knockdown of the endothelin-1-matrix metalloproteinase-1 pathway. 2080 48

The aim of this study was to investigate the effect and mechanism of Helicobacter pylori infection in the invasion and metastasis of gastric cancer. Specimens from 80 patients with gastric cancer (of which 20 patients had metastatic gastric cancer) and 40 patients with chronic gastritis were included in this study. H. pylori infection was determined by ELISA and the expression of matrix metalloproteinase-1 (MMP-1) and MMP-10 was observed using immunohistochemistry. The correlation between H. pylori infection and the clinical pathological features of gastric cancer was analyzed by SPSS 13.0 software. The protein expression levels of MMP-1 and MMP-10 in MGC-803 cells infected with H. pylori were analyzed using western blotting. H. pylori infection was found in 62 of the 80 patients with gastric cancer and in 13 of the 40 patients with chronic gastritis. In addition, H. pylori infection was correlated with the staging and lymph node metastasis, but not with the gender, age and histological types of patients. H. pylori infection was also significantly correlated with the expression of MMP-1 and MMP-10 (r=0.8718, P<0.05 and r=0.5477, P<0.05, respectively). The expression of MMP-1 and MMP-10 was significantly upregulated following induction by H. pylori infection (P<0.05), with significant effects occurring following infection for 12 and 6 h, respectively. H. pylori infection may promote the invasion and metastasis of gastric cancer by increasing the expression of MMP-1 and MMP-10.
 ...
PMID:Helicobacter pylori infection promotes the invasion and metastasis of gastric cancer through increasing the expression of matrix metalloproteinase-1 and matrix metalloproteinase-10. 2512 May 97