Strickland C L, Weber P C
Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA.
Curr Opin Drug Discov Devel. 1999 Sep;2(5):475-83.
Emerging therapies for the treatment of cancer rely on detailed knowledge of cell growth mechanisms. It is hoped that mechanism-based inhibitors will prove more effective and exhibit fewer side effects than current treatments. Among the first, non-cytotoxic anticancer agents to enter clinical trials are the farnesyl protein transferase inhibitors, which prevent attachment of the farnesyl isoprenoid side chain to Ras. This post-translational modification is essential for the function of Ras, a protein exhibiting unregulated activity in nearly one-third of human cancers. Here structural studies of farnesyl protein transferase and strategies for discovery of its inhibitors are reviewed.
癌症治疗的新兴疗法依赖于对细胞生长机制的详细了解。人们希望基于机制的抑制剂将比目前的治疗方法更有效，且副作用更少。最早进入临床试验的非细胞毒性抗癌药物之一是法尼基蛋白转移酶抑制剂，它可阻止法尼基类异戊二烯侧链与Ras蛋白结合。这种翻译后修饰对于Ras蛋白的功能至关重要，Ras蛋白在近三分之一的人类癌症中表现出不受调控的活性。本文综述了法尼基蛋白转移酶的结构研究及其抑制剂的发现策略。
