Abstract B35: Discovery of K-Ras(G12D)-targeting peptide KRpep-2d and its optimization strategy

Mutated Ras proteins play important roles in cell differentiation, proliferation, and survival of various cancers, especially mutations at residue Gly12 where G12D in K-Ras is the most frequent mutation. Although over 30 years have passed since the discovery of mutated Ras in human cancers, effective drug targeting to Ras has not been marketed. Very recently, KRpep-2d, an artificial cyclic peptide, was discovered as a first selective inhibitor to K-Ras(G12D) by phage display technology. KRpep-2d possesses low nanomol level activity in cell-free assays and shows preferable target selectivity in cell-based assay. In this presentation, I review the biochemical activity, biophysical activity, and SAR of KRpep-2d. In addition, I will discuss a strategy to brush up KRpep-2d for its therapeutic use. Citation Format: Kotaro Sakamoto. Discovery of K-Ras(G12D)-targeting peptide KRpep-2d and its optimization strategy [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr B35.