Marciano D, Ben-Baruch G, Marom M, Egozi Y, Haklai R, Kloog Y
Israel Institute for Biological Research, Ness Ziona.
J Med Chem. 1995 Apr 14;38(8):1267-72. doi: 10.1021/jm00008a004.
Inhibitors of the enzyme that methylates ras proteins, the prenylated protein methyltransferase (PPMTase), are described. They are farnesyl derivatives of rigid carboxylic acids that recognize the farnesylcysteine recognition domain of the enzyme but do not serve as substrates. They also inhibit ras-dependent cell growth by a mechanism that is probably unrelated to inhibition of ras methylation, even though their potencies as PPMTase inhibitors and cell-growth inhibitors correlate well. The most potent inhibitor is S-trans,trans-farnesylthiosalicylic acid (FTS) (2). FTS (2) selectively inhibits the growth of human Ha-ras-transformed Rat1 cells in vitro (EC50 = 7.5 microM).
本文描述了可甲基化Ras蛋白的酶——异戊二烯化蛋白甲基转移酶（PPMTase）的抑制剂。它们是刚性羧酸的法尼基衍生物，能识别该酶的法尼基半胱氨酸识别结构域，但不作为底物。它们还通过一种可能与抑制Ras甲基化无关的机制抑制Ras依赖性细胞生长，尽管它们作为PPMTase抑制剂和细胞生长抑制剂的效力具有良好的相关性。最有效的抑制剂是S-反式，反式-法尼基硫代水杨酸（FTS）（2）。FTS（2）在体外选择性抑制人Ha-Ras转化的Rat1细胞的生长（EC50 = 7.5 microM）。
