Fig. 3: Selectivity and cell activity of OGG1 inhibitors.
From: Virtual fragment screening for DNA repair inhibitors in vast chemical space
a Chemical structures of OGG1 inhibitors TH5487 and compound 23. b Inhibition of DNA repair enzymes (OGG1, SMUG1, APE1, NEIL1, MTH1, see Methods for abbreviations) by five OGG1 inhibitors. Mean IC50 values from three independent experiments are shown. Grey boxes indicate IC50 > 99 μM. c Shift in thermal stabilization of OGG1 in HL60 cells treated with OGG1 inhibitors. Mean values ± SEM from three independent experiments (dot plots) are shown. d Maximum fluorescence intensity of OGG1-GFP accumulation at laser-induced DNA damage sites after indicated treatments. Mean values of 15 cells for each condition from three independent experiments are shown. Statistical significance was determined using One-way Anova (p = 0.0092 for 10 μM compound 23, p < 0.0001 for 50 μM compound 23, and p = 0.0048 for TH5487). e Recruitment kinetics of OGG1-GFP to laser-induced DNA damage sites in U2OS cells after 1 h pre-treatment with compound 23 and TH5487. Results of 15 cells for each condition from three independent experiments are shown ± SEM. f Anti-inflammatory effect of TH5487 and compound 23 in NF-κB activation assay. Mean values ± SD from three independent experiments are shown. g The percentage cell viability of transformed and non-transformed cell lines upon treatment with different OGG1 inhibitors (100 μM). A2780, A549, and HCT116 represent ovarian, lung and colon cancer, respectively, and BJhTERT is a non-transformed control cell line. Mean values from two independent experiments are shown. h Cytotoxicity of TH5487 and compound 11 (Table 1) in A2780 and BJhTERT cell lines. Mean values from two independent experiments are shown. Source data are provided as a Source Data file.
