ISSN:
0730-2312
Keywords:
elastase inhibitors
;
β-lactams
;
lung damage
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
Human polymorphonuclear leukocyte elastase (PMN elastase) is inhibited by L-659, 286 (7α-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 μM. This inhibition is time-dependent, rapid, and only slowly reversible, with a t1/2 of 〉 3 days at 25°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.
Additional Material:
4 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcb.240390106
Permalink
