Pharmacological profile of the substituted beta-lactam L-659,286: a member of a new class of human PMN elastase inhibitors
| Autor: | Karen M. Hand, L. Schaeffer, Donald G. Osinga, Alan L. Maycock, Paul E. Finke, Richard A. Mumford, P. Davies, Pam S. Dellea, David Fletcher, C. P. Dorn, R. J. Bonney, T. Nolan, D. Frankenfield, Shrenik S. Shah, William K. Hagmann, Bonnie M. Ashe, James B. Doherty |
|---|---|
| Rok vydání: | 1989 |
| Předmět: |
Lung Diseases
Plasmin Neutrophils Thio Hemorrhage Pharmacology Cathepsin G Biochemistry chemistry.chemical_compound Thrombin Cricetinae medicine Animals Molecular Biology Chymotrypsin biology medicine.diagnostic_test Pancreatic Elastase Cell Biology Trypsin Cephalosporins Papain Bronchoalveolar lavage chemistry Callitrichinae biology.protein medicine.drug |
| Zdroj: | Journal of cellular biochemistry. 39(1) |
| ISSN: | 0730-2312 |
| Popis: | Human polymorphonuclear leukocyte elastase (PMN elastase) is inhibited by L-659,286 (7 alpha-methoxy-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4- triaz-in-3-yl)thio]methyl]-5-thia-1-aza-6R-bicyclo[4.2.O]oct-2-ene -2- pyrrolidine carboxamide-5,-dioxide) with a Ki of 0.4 microM. This inhibition is time-dependent, rapid, and only slowly reversible, with a t1/2 of greater than 3 days at 25 degrees C. L-659,286 is also highly selective for PMN elastase, as it does not inhibit thrombin, trypsin, papain, plasmin, chymotrypsin, or cathepsin G. L-659,286 administered intratracheally inhibits lung damage caused by administration via the same route of human PMN elastase into hamsters. In marmosets, L-659,286 is cleared from blood very rapidly after an intravenous injection but is recovered in bronchoalveolar lavage fluid for several hours after intratracheal administration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text