Soper David L, Sheville Justin, O'Neil Steven V, Wang Yili, Laufersweiler Michael C, Oppong Kofi A, Wos John A, Ellis Christopher D, Fancher Amy N, Lu Wei, Suchanek Maureen K, Wang Richard L, De Biswanath, Demuth Thomas P
Procter & Gamble Pharmaceuticals, Mason, OH 45040, USA.
Bioorg Med Chem Lett. 2006 Aug 15;16(16):4233-6. doi: 10.1016/j.bmcl.2006.05.076. Epub 2006 Jun 16.
Novel 1-(2-acylhydrazinocarbonyl)cycloalkyl carboxamides were designed as peptidomimetic inhibitors of interleukin-1beta converting enzyme (ICE). A short synthesis was developed and moderately potent ICE inhibitors were identified (IC(50) values <100 nM). Most of the synthesized examples were selective for ICE versus the related cysteine proteases caspase-3 and caspase-8, although several dual-acting inhibitors of ICE and caspase-8 were identified. Several of the more potent ICE inhibitors were also shown to inhibit IL-1beta production in a whole cell assay (IC(50) < 500 nM).
新型1-(2-酰肼羰基)环烷基羧酰胺被设计为白细胞介素-1β转化酶(ICE)的拟肽抑制剂。开发了一种简短的合成方法，并鉴定出中等效力的ICE抑制剂(IC(50)值<100 nM)。尽管鉴定出了几种ICE和半胱天冬酶-8的双效抑制剂，但大多数合成实例对ICE相对于相关半胱氨酸蛋白酶半胱天冬酶-3和半胱天冬酶-8具有选择性。几种效力更强的ICE抑制剂在全细胞试验中也显示出抑制IL-1β产生的作用(IC(50)<500 nM)。
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