Abstract
Activating Ras mutations are associated with ∼30% of all human cancers and the four Ras isoforms are highly attractive targets for anticancer drug discovery. However, Ras proteins are challenging targets for conventional drug discovery because they function through intracellular protein-protein interactions and their surfaces lack major pockets for small molecules to bind. Over the past few years, researchers have explored a variety of approaches and modalities, with the aim of specifically targeting oncogenic Ras mutants for anticancer treatment. This perspective will provide an overview of the efforts on developing "macromolecular" inhibitors against Ras proteins, including peptides, macrocycles, antibodies, nonimmunoglobulin proteins, and nucleic acids.
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