Design,Synthesis and Biological Evaluation of Sugar-Derived Ras Inhibitors

摘要

The design and synthesis of novel Ras inhibitors with a bicyclic scaffold derived from the natural sugar D-arabinose are presented.Molecular modelling showed that these ligands can bind Ras by accommodating the aromatic moieties and the phenylhydrox-ylamino group in a cavity near the Switch II region of the protein.All the synthetic compounds were active in inhibiting nucleotide exchange on p21 human Ras in vitro,and two of them selectively inhibited Ras-dependent cell growth in vivo.