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The effects of potential anti-osteoarthritic compounds both on the direct inhibition of collagenase and neutral protease activities and on IL-1 induced release of neutral proteases from rabbit articular chondrocytes were investigated. WY-46,135 ((+)-N-[[[(5-chloro-2-benzothiazolyl)thio]phenyl]acetyl]-L- cysteine) directly inhibited collagenase activity (IC50 = 15.4 microM). This inhibition was reversible upon dialysis. WY-46,135 also directly inhibited neutral protease activity (IC50 = 16.8 microM) but did not significantly block bacterial collagenase activity at a concentration of 80 microM. In contrast, WY-48,989 (4-[[2-(7-chloro-2-phenyl-2H-pyrazolo[4,3-c]quinolin-4- yl)ethyl]amino]benzonitrile) did not directly inhibit either collagenase (10 microM) or neutral protease (100 microM) activity. Both WY-48,989 and WY-46,135 inhibited IL-1 stimulated release of neutral proteases (IC50 = 3 microM). The activities of these compounds represents two potential approaches for the treatment of osteoarthritis. WY-46,135 combines direct metalloprotease inhibitory activity with the inhibition of IL-1 stimulated neutral protease release from articular chondrocytes while WY-48,989 selectively inhibits the IL-1 induced release of metalloproteases.
R G Caccese, and
J F DiJoseph, and
J S Skotnicki, and
L E Borella, and
L M Adams
December 1986,
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R G Caccese, and
J F DiJoseph, and
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L E Borella, and
L M Adams
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Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences,
R G Caccese, and
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R G Caccese, and
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R G Caccese, and
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The Tohoku journal of experimental medicine,
R G Caccese, and
J F DiJoseph, and
J S Skotnicki, and
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L M Adams
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FEBS letters,
R G Caccese, and
J F DiJoseph, and
J S Skotnicki, and
L E Borella, and
L M Adams
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Experimental cell research,
R G Caccese, and
J F DiJoseph, and
J S Skotnicki, and
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L M Adams
November 1987,
Biochemistry international,
R G Caccese, and
J F DiJoseph, and
J S Skotnicki, and
L E Borella, and
L M Adams
October 1989,
Biochemical and biophysical research communications,
R G Caccese, and
J F DiJoseph, and
J S Skotnicki, and
L E Borella, and
L M Adams
June 1989,
Agents and actions,
