Pharmacological studies of FUT-175, nafamstat mesilate. I. Inhibition of protease activity in in vitro and in vivo experiments.

@article{Aoyama1984PharmacologicalSO,
  title={Pharmacological studies of FUT-175, nafamstat mesilate. I. Inhibition of protease activity in in vitro and in vivo experiments.},
  author={Takuo Aoyama and Yoshitaka Ino and Masayuki Ozeki and Minoru Oda and Takayuki Sato and Yoshiko Koshiyama and S. Suzuki and M. Fujita},
  journal={Japanese journal of pharmacology},
  year={1984},
  volume={35 3},
  pages={
          203-27
        }
}
FUT-175, 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate (nafamstat mesilate), a novel synthetic protease-inhibiting agent, was studied to determine its in vitro effects against various proteases and other enzymes, as well as to determine its in vivo protease inhibitory effects. FUT-175 was found to inhibit, in an intense, specific and reversible way, the enzyme activities of trypsin, C1r, C1s, thrombin, kallikrein and plasmin with IC50 values of the order of 10(-6)-10(-8) M. FUT… 
The effect of FUT-175 (Nafamstat Mesilate) on C3a, C4a and C5a generation in vitro and inflammatory reactions in vivo.
TLDR
Although FUT-175 is a potent inhibitor of C3a, C4a and C5a generation, it has novel and broad anti-inflammatory effects, possibly through actions in addition to complement inhibition as indicated by inhibition of FNLP-, LTB4- and ZAP-induced reactions.
Pharmacological studies of FUT-175, nafamostat mesilate. V. Effects on the pancreatic enzymes and experimental acute pancreatitis in rats.
TLDR
Data strongly support that FUT-175 is clinically useful in the therapy of acute pancreatitis and reduces the mortality of rats in the experimental acute pancreas in a dose-dependent manner.
Inhibitory effects of newly synthesized active center-directed trypsin-like serine protease inhibitors on the complement system
TLDR
Data suggest that the 2-furylcarboxylic acid derivatives have a strong potential for inhibiting the activities of the complement, and the guanidino group was required to retain high inhibitory activities in vivo, and compound 7 is a hopeful anti-complement agent.
Pharmacological studies on 6-amidino-2-naphthyl[4-(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethane sulfonate (FUT-187). I: Inhibitory activities on various kinds of enzymes in vitro and anticomplement activity in vivo.
TLDR
FUT-187 should be a more potent oral therapeutic agent than FUT-175 for various inflammatory diseases attributed to the excessive activation of the complement system followed by platelet aggregation.
Effects of FUT-175, a novel synthetic protease inhibitor, on the development of adjuvant arthritis in rats and some biological reactions dependent on complement activation.
TLDR
The results suggest that the anti-inflammatory activity of FUT-175 may differ from indomethacin in the mechanisms of action and, at least in part, due to theAnti-complement activity.
Effect of nafamostat mesilate, a synthetic protease inhibitor, on tissue factor-factor VIIa complex activity.
TLDR
Findings suggested that NM may be a potent inhibitor of TF-F.VIIa complex and the therapeutic effect of NM in DIC patients could be partly explained by inhibition of the extrinsic pathway of the coagulation system.
Inhibitory effects of FUT-175, a new synthetic protease inhibitor, on intravascular hemolysis by human serum in mice.
TLDR
Results indicated that FUT-175 prevents intravascular hemolysis of mouse erythrocytes through the inhibitory effect of both alternative and classical complement pathway.
The effects of nafamostat mesilate (FUT-175) on caerulein-induced acute pancreatitis in the rat
  • J. Wisner, S. Ozawa, I. Renner
  • Medicine
    International journal of pancreatology : official journal of the International Association of Pancreatology
  • 1989
TLDR
Data indicate that serine proteases appear to be involved in the pathogenesis of CR induced AP in rats and that FUT-175 administered in low doses (2.5–10.0 mg/kg/h) provides significant protection against this form of pancreatitis.
Protective effect of nafamostat mesilate
SummaryThis in vivo and in vitro study demonstrates the protective effects of a new synthetic protease inhibitornafamostat mesilate, FUT-175—on increased cellular and lysosomal fragility within
A Synthetic Serine Protease Inhibitor, Nafamostat Mesilate, Is a Drug Potentially Applicable to the Treatment of Ebola Virus Disease.
TLDR
In vitro and in vivo experiments using active EBOV to examine the activities of NM against the infection and the DIC induced by the infection are advocated and trials for comparison among anti-DIC drugs including the NM are suggested in parallel with the experiments.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 36 REFERENCES
Inhibition of various immunological reactions in vivo by a new synthetic complement inhibitor.
  • Y. Hitomi, S. Fujii
  • Chemistry, Medicine
    International archives of allergy and applied immunology
  • 1982
TLDR
FUT-175 strongly inhibited complement-medicated hemolysis via the classical and alternative pathways and inhibited other immunological reactions, such as passive cutaneous anaphylaxis and delayed hypersensitivity, and strongly protected mice from death in endotoxin shock.
Complement inhibition by amidines and guanidines--in vivo and in vitro results.
TLDR
It is concluded that this class of inhibitors must undergo structural modifications designed to produce adequate and sustained plasma concentrations before in vivo anticomplementary activity can be expected.
New synthetic inhibitor to the alternative complement pathway.
TLDR
6-amidino-2-naphthyl 4-guanidinobenzoate was a non-competitive inhibitor of the esterolysis of L-leucyl-L-alanyl- L-arginine naphthylester by factor B and CVF X Bb.
Role of fumaropimaric acid in guinea pig complement dependent and non-complement dependent biologic reactions. I. Inhibition of Forssman, reversed passive arthus, and PCA reactions by fumaropimaric acid.
TLDR
Evidence is cited that makes it unlikely that the demonstrated direct antihistaminic effect of fumaropimaric acid is responsible for the suppression of the PCA, and indicates a block in the in vivo reaction beyond the C′3 step.
Inhibition of the alternative pathway of complement by gold sodium thiomalate in vitro.
TLDR
AuTM is most active in inhibiting convertase formation on cellular intermediates bearing the lowest number of 125 I-C3b per cell and requiring development with the highest B concentration, suggesting the binding site on C3b for B as the locus of AuTM action.
An anticomplementary agent, K-76 monocarboxylic acid: its site and mechanism of inhibition of the complement activation cascade.
A monocarboxylic acid derivative (K-76 COOH) of K-76, purified from the culture filtrate of Stachybotrys complement I nov. sp. K-76, inhibits complement (C) activity. Its inhibitory action is mainly
Effect of anti‐proteases and hexadimethrine bromide on the release of a bradykinin‐like substance during heating (46° C) of rat paws
TLDR
It is suggested that heating elicits a process leading to plasma extravasation and that the subcutaneous tissue is the chief site of release of the active material.
New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin.
TLDR
6'-amidino-2-naphthyl-4-guanidinobenzoate dihydrochloride, 4-(beta- amidinoethenyl)phenyl- 4-guAnidin Obenzoates dimethanesulfonate and 4-amidinos2-benzoylphenyl the most effective inhibitors of trypsin, plasmin, pancreatic kallikrein and thrombin.
Measurement of the rate of plasmin action on synthetic substrates.
  • P. S. Roberts
  • Medicine, Biology
    The Journal of biological chemistry
  • 1958
TLDR
The Hestrin method is modified so that enzyme rates at optimal substrate concentrations of either TAME or LME can be determined by using the same standard reagents and procedures and the rate measurements are reproducible with an average deviation of 3 per cent of the rate.
New Fluorogenic Substrates for α-Thrombin, Factor Xa, Kallikreins, and Urokinase
: Twenty peptide-4-methylcoumarin amides (MCA) were newly synthesized and tested as possible substrates for alpha-thrombin, factor Xa, kallikreins, urokinase, and plasmin. These fluorogenic peptides
...
1
2
3
4
...