Generation of KS-58 as the first K-Ras(G12D)-inhibitory peptide presenting anti-cancer activity in vivo

• Published in: Scientific Reports Vol. 10; no. 1; pp. 21671 - 16
• Main Authors: Sakamoto, Kotaro, Masutani, Teruaki, Hirokawa, Takatsugu
• Format: Journal Article
• Language: English
• Published: London Springer Science and Business Media LLC 10.12.2020; Nature Publishing Group UK; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154; 631/67; Amino Acid Sequence; Amino acids; Animals; Antineoplastic Agents; Cancer therapies; Cell Line, Tumor; Cell Proliferation; Cell Proliferation - drug effects; Cell Proliferation - genetics; Chemotherapy; Deoxycytidine; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Drug delivery; Drug development; Drug Therapy, Combination; Gemcitabine; Genes, ras; Genes, ras - genetics; H-Ras protein; Humanities and Social Sciences; Intravenous administration; K-Ras protein; Lung cancer; Lung Neoplasms; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Medicine; Mice; Molecular Targeted Therapy; multidisciplinary; Mutation; Neoplasm Transplantation; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Peptides; Peptides - administration & dosage; Peptides - chemistry; Peptides - pharmacology; Protein interaction; Q; R; Ras protein; Rats; Science; Science (multidisciplinary); Therapeutic targets; Xenografts

Ras mutations (e.g., occur in K-Ras, N-Ras, and H-Ras) are one of the most desirable and promising drug targets in chemotherapy treatments for cancer. However, there are still no approved drugs directly targeting mutated Ras. In 2017, an artificial cyclic peptide, KRpep-2d, was discovered as the fir...