Direct inhibition of oncogenic RAS using Cell-Permeable Fusion Proteins

Fusion protein drug with RAS-binding domain and cell-permeable peptide blocks binding between RAS-GTP and RAS-effectors.


➢ Novel anti-cancer drug candidates specifically inhibiting the majority of RAS mutants

Background and Technology

Oncogenic RAS proteins are extremely difficult targets for rational drug discovery. No clinical inhibitor is available for the majority of RAS mutants.

RAS proteins lack well-defined molecular pockets on their molecular surface for small molecule compounds. Naturally, macromolecules have suffered from low permeability of the cell membrane.
To solve the problem, we strategically designed 51 fusion proteins with RAS binding domains (RBDs) and cell-permeable peptides (CPPs), and identified the most effective fusion protein “Protein C” by cell-based screening.


  • Protein C demonstrated comparable IC50 with existing small-molecule RAS inhibitor BI2852 in cell-based assay.
  •  Protein C reduces cancer cell-viability and inhibits RAS signals in several KRAS-mutant cell lines


JP 2020-137653 (unpublished)


Gifu University, Tokai National Higher Education and Research System

Progress and Future Plan

  • Currently lacking in vivo evidence of activity.
  • Primary goal is optimization of Protein C to prove in vivo activity in mouse model.
  • We are looking for sponsoring or collaborative partners (e.g. affinity maturation and liposome encapsulation).
  • We can synthesize and evaluate designed proteins.

Product No. BK-03492

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