Abstract ▼ AI-Helper

The oncogenic KRAS has been the target of drug development because it is the frequently mutated oncogene in human cancers. However, many drugs have a lower affinity for mutated KRAS proteins, so identifying effective direct-binding agents has been difficult. A novel tumor suppressor H-REV107 peptide...

The oncogenic KRAS has been the target of drug development because it is the frequently mutated oncogene in human cancers. However, many drugs have a lower affinity for mutated KRAS proteins, so identifying effective direct-binding agents has been difficult. A novel tumor suppressor H-REV107 peptide was developed that a high-affinity direct interaction between KRAS G12V and H-REV107 peptide. The crystal structure of KRAS G12V-H-REV107 peptide complex was determined. H-REV107 peptide interacts with KRAS G12V in the GDP-bound inactive state and to form a stable complex, that blocks the activation of KRAS. H-REV107 peptide acts as an inhibitor of mutant KRAS protein by [α-32P] GTP binding assays. The H-REV107 peptide inhibits cell proliferation in pancreatic cancer and colon cancer cell lines. Specifically, the H-REV107 peptide can suppresses pancreatic tumor growth by reducing tumor volume and weight in xenotransplantation mouse models. The results presented herein will facilitate the development of novel drugs for inhibition of KRAS mutations in cancer patients.