Inhibition of metalloproteinase activity of rheumatoid arthritis synovial cells by a new inhibitor [BE16627B; L-N-(N-hydroxy-2-isobutylsuccinamoyl)-seryl-L-valine].
The effect of a new metalloproteinase (MP) inhibitor [BE16627B; L-N-(N-hydroxy-2-isobutylsuccinamoyl)-seryl-L-valine, MW: 375.2] isolated from Streptomyces sp. was evaluated by using primary cultures of synovial cells from rheumatoid arthritis patients. BE16627B selectively inhibited MPs such as human stromelysin and 92 kD gelatinase. After the cells were cultured with BE16627B for 5 days, BE16627B inhibited MP activity in the primary culture supernatants from synovial cells in a dose-dependent fashion without showing apparent cytotoxicity or affecting the production and secretion of MPs. Its IC50 for active collagenolysis before activation by trypsin was 25 microM.
Naito
K
K
Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Japan.
Nakajima
S
S
Kanbayashi
N
N
Okuyama
A
A
Goto
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004151:Dipeptides / Q000494:pharmacology*; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D011480:Protease Inhibitors / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology*; D013582:Synovial Fluid / Q000166:cytology / Q000201:enzymology*; D014407:Tumor Cells, Cultured
D004151:Dipeptides; D011480:Protease Inhibitors; D013386:Succinates; C085667:L-N-(N-hydroxy-2-isobutylsuccinamoyl)seryl-L-valine; D010450:Endopeptidases; D008666:Metalloendopeptidases