Author/Authors :
John L. Gilmore، نويسنده , , Bryan W. King، نويسنده , , Cathy Harris، نويسنده , , Thomas Maduskuie، نويسنده , , Stephen E. Mercer، نويسنده , , Ruiqin Liu، نويسنده , , Maryanne B. Covington، نويسنده , , Mingxin Qian، نويسنده , , Maria D. Ribadeneria، نويسنده , , Krishna Vaddi، نويسنده , , James M. Trzaskos، نويسنده , , Robert C. Newton، نويسنده , , Carl P. Decicco، نويسنده , , James J. -W. Duan، نويسنده ,
Abstract :
A novel series of achiral TNF-α converting enzyme (TACE) inhibitors has been discovered. These compounds exhibited activities from 0.35 to 11 nM in a porcine TACE assay and inhibited TNF-α production in an LPS-stimulated whole blood assay with an IC50 value of 23 nM for the most potent one. They also have excellent selectivities over related metalloproteases including aggrecanases.
Keywords :
Antiinflammatory , Hydroxamic acid , TACE inhibitors , Metazincin , metalloprotease , Sheddase , tumor necrosis factor
