Wai J S, Bamberger D L, Fisher T E, Graham S L, Smith R L, Gibbs J B, Mosser S D, Oliff A I, Pompliano D L, Rands E
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486.
Bioorg Med Chem. 1994 Sep;2(9):939-47. doi: 10.1016/s0968-0896(00)82043-x.
Replacement of the central amino methylene linkage of C[psi CH2NH]A[psi CH2NH]AX tetrapeptide inhibitors with carbon tethers led to compounds with potency in the nanomolar range. Some of the more potent olefinic compounds inhibit Ras processing in intact v-ras transformed NIH 3T3 cells with IC50 values in the 0.1 to 1 microM range, and inhibit selectively the anchorage-independent growth of H-ras transformed Rat1 cells at 10 microM.
将C[ψCH2NH]A[ψCH2NH]AX四肽抑制剂的中心氨基亚甲基连接替换为碳链连接，得到了具有纳摩尔级效力的化合物。一些效力更强的烯烃类化合物在完整的v-ras转化的NIH 3T3细胞中抑制Ras加工，IC50值在0.1至1微摩尔范围内，并在10微摩尔时选择性抑制H-ras转化的Rat1细胞的非锚定依赖性生长。
