Title:Direct Inhibitors of Ras-Effector Protein Interactions
VOLUME: 16 ISSUE: 5
Author(s):Punit Upadhyaya, Walaa Bedewy and Dehua Pei
Affiliation:Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States.
Keywords:Cancer, Cell signaling, Inhibition, Macrocycles, Protein-protein interaction, Ras.
Abstract:Activating Ras mutations are associated with ~30% of all human cancers, which often
respond poorly to standard therapies. The four Ras isoforms are therefore highly attractive targets for
anticancer drug discovery. However, Ras proteins function through protein-protein interactions and
their surfaces lack any major pockets for small molecules to bind; as a result they have been declared
“undruggable” for the past 30 years. Several breakthroughs during the past few years may finally
remove Ras from the list of undruggable proteins. This mini-review discusses the current approaches
to developing inhibitors especially cyclic peptides that physically block the interaction between Ras and its downstream
effector proteins, which is potentially the most effective approach for treating Ras mutant cancers.
