FIGURE 2 from DNA2 Nuclease Inhibition Confers Synthetic Lethality in Cancers with Mutant p53 and Synergizes with PARP Inhibitors
Year: 2023
Type: other
Abstract: Cytotoxic effects of DNA2 inhibitor C5 and its analogs in human cancer cells. A, Molecular docking of C5 or its analog d16 in the Site 1 pocket of DNA2. A, C5 chemical structure and its docking score. B and C, The three-dimensional structure of DNA2 with C5 docked in the Site 1 pocket, surface view and cartoon view. D, Crystal structure of DNA2 in complex with an ssDNA (PDB: 5EAX; ref. 37). E, The positions of DNA and C5 in DNA2. F–I, The lowest-energy docking positions of d16, d11, d18, and d24 in DNA2 show potential interference with the passage of DNA strand (orange dotted line). B, Chemical structures of C5 analogs and their docking scores in DNA2. MDA-MB-468, BT549, and MDAH-2774 cells were treated for 72 hours with 20 µmol/L of one of the 24 C5 analogs (C) or with increasing concentrations of C5 or d16 (D). Cell proliferation was measured by MTT assay. The data shown represent mean ± SD (n = 3 biological replicates). *, P < 0.05 indicating statistically significant difference between vehicle (Veh) and C5 analogs (two-tailed t test). E, Structure-activity relationship analysis identifies the core structure of the active compounds.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4387687405