biostudies-literatureUnknown11(5)Li LPhosphorylation 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 cabozanACS omega7974-7987https://www.ebi.ac.uk/biostudies/studies/S-EPMC12902871biostudies-literatureComputational and Experimental Verification of Cabozantinib Targeting DDX11 to Inhibit DNA Damage Repair in Liver Cancer.PMC12902871Liu ZLiu LHuang ZLi DZhong JLi LfalseComputational and Experimental Verification of Cabozantinib Targeting DDX11 to Inhibit DNA Damage Repair in Liver Cancer.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 cabozan2026-01-01T00:00:00Z2026 Feb2026-07-15T18:05:48.888Z2026-07-08T03:08:31.726ZS-EPMC129028714169627510.1021/acsomega.5c10093