Singh S B, Zink D L, Williams M, Polishook J D, Sanchez M, Silverman K C, Lingham R B
Merck Research Laboratories, Rahway, NJ 07065, USA.
Bioorg Med Chem Lett. 1998 Aug 18;8(16):2071-6. doi: 10.1016/s0960-894x(98)00371-0.
Farnesyl-protein transferase (FPTase) is a critical enzyme that participates in the post-translational modification of the Ras protein. Inhibitors of this enzyme have the potential of being novel anticancer agents for tumors in which the ras oncogene is found mutated and contributes to cell transformation. Continued screening of natural product extracts led to the isolation of kampanols, which are novel and specific inhibitors of FPTase. The most active kampanols exhibited IC50 values between 7 to 13 microM against human recombinant FPTase. The isolation, structure determination, and biological activity of these compounds are described.
法尼基蛋白转移酶（FPTase）是一种关键酶，参与Ras蛋白的翻译后修饰。该酶的抑制剂有可能成为针对ras癌基因发生突变并导致细胞转化的肿瘤的新型抗癌药物。对天然产物提取物的持续筛选导致了坎帕醇的分离，坎帕醇是FPTase的新型特异性抑制剂。活性最强的坎帕醇对人重组FPTase的IC50值在7至13微摩尔之间。本文描述了这些化合物的分离、结构测定和生物活性。
