Multi-targeting of K-Ras domains and mutations by peptide and small molecule inhibitors.

ABSTRACT: K-Ras activating mutations are significantly associated with tumor progression and aggressive metastatic behavior in various human cancers including pancreatic cancer. So far, despite a large number of concerted efforts, targeting of mutant-type K-Ras has not been successful. In this regard, we aimed to target this oncogene by a combinational approach consisting of small peptide and small molecule inhibitors. Based on a comprehensive analysis of structural and physicochemical properties of predominantly K-Ras mutants, an anti-cancer peptide library and a small molecule library were screened to simultaneously target oncogenic mutations and functional domains of mutant-type K-Ras located in the P-loop, switch I, and switch II regions. The selected peptide and small molecule showed notable bi

SUBMITTER: Poorebrahim M 

PROVIDER: S-EPMC9041843 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature