Identification of Dietary Bioflavonoids as Potential Inhibitors against KRAS G12D Mutant-Novel Insights from Computer-Aided Drug Discovery.

ABSTRACT: The KRAS G12D mutation is very frequent in many cancers, such as pancreatic, colon and lung, and has remained undruggable for the past three decades, due to its smooth surface and lack of suitable pockets. Recent small pieces of evidence suggest that targeting the switch I/II of KRAS G12D mutant could be an efficient strategy. Therefore, in the present study, we targeted the switch I (residues 25-40) and switch II (residues 57-76) regions of KRAS G12D with dietary bioflavonoids in comparison with the reference KRAS SI/II inhibitor BI-2852. Initially, we screened 925 bioflavonoids based on drug-likeness properties, and ADME properties and selected 514 bioflavonoids for further studies. Molecular docking resulted in four lead bioflavonoids, namely 5-Dehydroxyparatocarpin K (L1), Carpachromen

SUBMITTER: Ramalingam PS 

PROVIDER: S-EPMC10047893 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature