Author/Authors :
James J. -W. Duan، نويسنده , , Lihua Chen، نويسنده , , Zhonghui Lu، نويسنده , , Bin Jiang، نويسنده , , Naoyuki Asakawa، نويسنده , , James E. Sheppeck II، نويسنده , , Ruiqin Liu، نويسنده , , Maryanne B. Covington، نويسنده , , William Pitts، نويسنده , , Soong-Hoon Kim، نويسنده , , Carl P. Decicco، نويسنده ,
Abstract :
Using a pyrimidine-2,4,6-trione motif as a zinc-binding group, a series of selective inhibitors of tumor necrosis factor-α converting enzyme (TACE) was discovered. Optimization of initial lead 1 resulted in a potent inhibitor (51), with an IC50 of 2 nM in a porcine TACE assay. To the best of our knowledge, compound 51 and related analogues represent first examples of non-hydroxamate-based inhibitors of TACE with single digit nanomolar potency.
