- Discovery of low nanomolar non-hydroxamate inhibitors of tumor necrosis factor-alpha converting enzyme (TACE).
Discovery of low nanomolar non-hydroxamate inhibitors of tumor necrosis factor-alpha converting enzyme (TACE).
Bioorganic & medicinal chemistry letters (2006-10-10)
James J-W Duan, Lihua Chen, Zhonghui Lu, Bin Jiang, Naoyuki Asakawa, James E Sheppeck, Rui-Qin Liu, Maryanne B Covington, William Pitts, Soong-Hoon Kim, Carl P Decicco
PMID17027261
초록
Using a pyrimidine-2,4,6-trione motif as a zinc-binding group, a series of selective inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) was discovered. Optimization of initial lead 1 resulted in a potent inhibitor (51), with an IC(50) 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.
MATERIALS