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Chemical Compound Review:

SureCN7859156 N'-(4-chlorophenyl)sulfonyl- N-[(1S)-2...

Synonyms: Ici 200880, Ici 200,880, AC1L1S7H, AC1Q3O4D, 105080-50-0

Mehta, J.L. et al., Davis, P.C. et al., Edwards, P.D. et al., Nicolini, F.A. et al., Edwards, P.D. et al.

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Disease relevance of Ici 200880

In the present study, we examined the effects of tissue-plasminogen activator (t-PA, 1 mg/kg over 20 minutes) given intravenously with either saline or a leukocyte elastase inhibitor (ICI 200,880, 5 mg/kg) in dogs with electrically-induced coronary artery thrombosis [1].

High impact information on Ici 200880

Currently ICI 200,880 is the only low molecular-weight HNE inhibitor known to be undergoing clinical trials, and may be the compound which finally demonstrates the clinical utility of a synthetic HNE inhibitor [2].
Ten minutes before reperfusion, dogs were randomly given saline or the neutrophil elastase inhibitor ICI 200,880 (10 mg.kg-1) and treatment was continued for the next 70 min [3].
Neutrophil elastase inhibitor ICI 200,880 protects against attenuation of coronary flow reserve and myocardial dysfunction following temporary coronary artery occlusion in the dog [3].
Flow cytometry also showed diminished neutrophil infiltration and oxidative burst in reperfused myocardium of ICI 200,880 treated (v saline treated) dogs [3].
An hydroxysuccinimide ester analogue of ICI 200,880 was coupled to the lysine residues of bovine serum albumin, characterized by gel electrophoresis and injected into rabbits to stimulate antibody formation; a highly specific, high titre antibody was obtained [4].

Anatomical context of Ici 200880

In contrast, neutrophil infiltration was minimal in the ICI 200,880 treated dogs, in spite of myocardial injury [3].

Associations of Ici 200880 with other chemical compounds

Previously we had shown that tripeptidyl trifluoromethyl ketones (TFMKs) possessing an N-terminal diarylacylsulfonamide, such as ICI 200,880 and ICI 200,355, displayed unparalleled protection against the lung damage induced by human neutrophil elastase (HNE) when the inhibitors were administered intratracheally [5].

Analytical, diagnostic and therapeutic context of Ici 200880

A specific radioimmunoassay for the measurement of ICI 200,880, an elastase inhibitor, in human serum [4].

References

Leukocyte elastase inhibition and t-PA-induced coronary artery thrombolysis in dogs: beneficial effects on myocardial histology. Nicolini, F.A., Mehta, J.L., Nichols, W.W., Donnelly, W.H., Luostarinen, R., Saldeen, T.G. Am. Heart J. (1991) [Pubmed]
Synthetic inhibitors of elastase. Edwards, P.D., Bernstein, P.R. Medicinal research reviews. (1994) [Pubmed]
Neutrophil elastase inhibitor ICI 200,880 protects against attenuation of coronary flow reserve and myocardial dysfunction following temporary coronary artery occlusion in the dog. Mehta, J.L., Nichols, W.W., Nicolini, F.A., Hendricks, J., Donnelly, W.H., Saldeen, T.G. Cardiovasc. Res. (1994) [Pubmed]
A specific radioimmunoassay for the measurement of ICI 200,880, an elastase inhibitor, in human serum. Davis, P.C., Wildonger, R.A., Veale, H.S. Journal of pharmaceutical and biomedical analysis. (1993) [Pubmed]
Discovery and biological activity of orally active peptidyl trifluoromethyl ketone inhibitors of human neutrophil elastase. Edwards, P.D., Andisik, D.W., Bryant, C.A., Ewing, B., Gomes, B., Lewis, J.J., Rakiewicz, D., Steelman, G., Strimpler, A., Trainor, D.A., Tuthill, P.A., Mauger, R.C., Veale, C.A., Wildonger, R.A., Williams, J.C., Wolanin, D.J., Zottola, M. J. Med. Chem. (1997) [Pubmed]

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