L-N6-(1-iminoethyl)lysine: a selective inhibitor of inducible nitric oxide synthase.
L-N6-(1-Iminoethyl)lysine (L-NIL) has been synthesized and is shown to be both a potent and selective inhibitor of mouse inducible nitric oxide synthase (miNOS). L-NIL has an IC50 of 3.3 microM for miNOS compared to an IC50 of 92 microM for rat brain constitutive NOS indicating that L-NIL is 28-fold more selective for inducible NOS. L-N5-(1-Iminoethyl)ornithine (L-NIO), which differs from L-NIL by having one less methylene group, has very similar potency for inducible NOS, but lacks selectivity. DL-N7-(1-Iminoethyl)homolysine was also synthesized and found to be substantially less potent than L-NIL or L-NIO, with intermediate selectivity for inducible NOS. These data suggest that L-NIL may be useful as a selective inhibitor of inducible NOS for determining the role of this enzyme in disease models.
Moore
W M
WM
Department of Inflammatory Diseases Research, G. D. Searle Research and Development, Monsanto Company, St. Louis, Missouri 63167.
Webber
R K
RK
Jerome
G M
GM
Tjoeng
F S
FS
Misko
T P
TP
Currie
M G
MG
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000201:enzymology; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D019001:Nitric Oxide Synthase; D051381:Rats
C090663:N(6)-(1-iminoethyl)lysine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D008239:Lysine