Non-covalent inhibitors of the 20S proteasome

被引：1
|
作者：
García-Echeverría, C [1 ]
Imbach, P [1 ]
Roesel, J [1 ]
Fuerst, P [1 ]
Lang, M [1 ]
Guagnano, V [1 ]
Noorani, M [1 ]
Zimmermann, J [1 ]
Furet, P [1 ]
机构：
[1] Novartis Pharma AG, Oncol Res, CH-4002 Basel, Switzerland
来源：
CHIMIA | 2003年 / 57卷 / 04期
关键词：
antitumor agents; drug design; enzyme inhibitors; peptidomimetic;
D O I：
10.2533/000942903777679415
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Peptidomimetics have been commonly used as lead compounds to design inhibitors with high affinity and specificity for a particular enzyme. The discovery that a 2-aminobenzylstatine derivative originally designed to target an aspartyl protease was able to inhibit specifically and non-covalently the chymotrypsin-like activity of the 20S proteasome represented a unique starting point for our medicinal chemistry endeavor for this target. Utilizing a structure-based design approach, we have been able to improve the potency of this new class of proteasome inhibitors without affecting its in vitro selectivity profile.
引用
收藏
页码：179 / 181
页数：3
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