Holms J, Mast K, Marcotte P, Elmore I, Li J, Pease L, Glaser K, Morgan D, Michaelides M, Davidsen S
Cancer Research Area, Abbott Laboratories, Dept. 47J, Bldg. AP10, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
Bioorg Med Chem Lett. 2001 Nov 19;11(22):2907-10. doi: 10.1016/s0960-894x(01)00603-5.
Modification of the P(1)' substituent of macrocyclic matrix metalloproteinase (MMP) inhibitors provided compounds that are selective for inhibition of tumor necrosis factor-alpha converting enzyme (TACE) over MMP-1 and MMP-2. Several analogues potently inhibited the release of TNF-alpha in a THP-1 cellular assay. Compounds containing a trimethoxyphenyl group in the P(1)' substituent demonstrated TACE selectivity across several series of hydroxamate-based inhibitors.
大环基质金属蛋白酶（MMP）抑制剂P(1)'取代基的修饰产生了对肿瘤坏死因子-α转化酶（TACE）具有选择性抑制作用的化合物，其选择性高于对MMP-1和MMP-2的抑制作用。在THP-1细胞试验中，几种类似物有效抑制了肿瘤坏死因子-α的释放。在基于异羟肟酸的一系列抑制剂中，P(1)'取代基含有三甲氧基苯基的化合物表现出对TACE的选择性。
