Jayasuriya H, Silverman K C, Zink D L, Jenkins R G, Sanchez M, Pelaez F, Vilella D, Lingham R B, Singh S B
Natural Products Drug Discovery, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA.
J Nat Prod. 1998 Dec;61(12):1568-70. doi: 10.1021/np980200c.
Farnesyl-protein transferase (FPTase) catalyses the specific transfer of farnesyl to Ras-peptides that is essential for oncogenic activity in oncogene-mediated tumors. Specific inhibition of FPTase activity has been shown to reduce tumor development in nude mice challenged with oncogenic forms of ras, thereby establishing FPTase as a viable therapeutic target. Our continued efforts to discover inhibitors of FPTase has led to the discovery of a triterpenoidal inhibitor, clavaric acid (1). This compound inhibits rHFPTase with an IC50 value of 1.3 microM. Structure elucidation, structure modifications, and biological activity of clavaric acid are herein described.
法尼基蛋白转移酶（FPTase）催化法尼基向Ras肽的特异性转移，这对于癌基因介导的肿瘤中的致癌活性至关重要。已证明特异性抑制FPTase活性可减少用致癌形式的ras攻击的裸鼠中的肿瘤发展，从而确立FPTase作为可行的治疗靶点。我们持续致力于发现FPTase抑制剂，已导致发现一种三萜类抑制剂，棒酸（1）。该化合物以1.3微摩尔的IC50值抑制重组人FPTase（rHFPTase）。本文描述了棒酸的结构解析、结构修饰和生物活性。
