α-Cyanocinnamide derivatives: A new family of non-peptide, non-sulfhydryl inhibitors of ras farnesylation

Article abstract of DOI:10.1016/S0968-0896(99)00118-2

Farnesylation of Ras and other proteins is required for their membrane attachment and normal function. Here we report on the synthesis of α-cyanocinnamide derivatives, a new family of farnesyltransferase inhibitors. These compounds are nonpeptidic and do not contain sulfhydryl groups. The most potent compound is a pure competitive inhibitor with respect to the Ras protein and mixed competitive with respect to farnesyl diphosphate. Selectivity studies against geranylgeranyltransferase and biological activities of selected compounds are described. Copyright (C) 1999.