Computational and Experimental Verification of Cabozantinib Targeting DDX11 to Inhibit DNA Damage Repair in Liver Cancer.

ABSTRACT: Phosphorylation of serine residues within SQ/TQ motifs, particularly Ser237 of the ATP-dependent DNA helicase DDX11, by ataxia telangiectasia mutated (ATM) kinase plays a key role in activating the DNA damage response (DDR) in liver cancer. To disrupt this signaling pathway, we applied a computationally guided drug repurposing approach to identify FDA-approved compounds capable of targeting critical DDX11 residues. A library of 2367 drugs was screened using a structure-based, site-specific docking strategy, yielding seven candidates with binding affinities from -6.5 to -7.7 kcal/mol. Although Afatinib showed the strongest docking score (-7.674 kcal/mol), it lacked hydrogen-bond interactions with Ser237 and Gln238 and was therefore excluded. In contrast, dacomitinib, ergotamine, and cabozan

SUBMITTER: Li L 

PROVIDER: S-EPMC12902871 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature