Search for: [Abstract = "rs. The first part of research was focused on searching for new CBR1 inhibitors. Optimization of two crystal structures \(PDB codes\: 1WMA and 3BHJ\) was performed. The structures differed in the presence of glutathione within the active site of CBR1. Using several optimization \(Induced\-fit docking, flexible docking, molecular dynamics\) and evaluation \(retrospective virtual screening\) methods, two CBR1 models \(1WMA_A3 and 3BHJ_N1\) were selected. They were then used to dock a library of over 2.3 million compounds in prospective virtual screening. 9 chemotypes of new potential CBR1 inhibitors were selected and then evaluated in CBR1 inhibition assay. Among them the most effective was a derivative of 2\-phenyl\-3,4\-dihydroquinazolin\-4\-one \(compound C2, IC50 = 7,56 μM\). Further structure optimization led to discovery of more CBR1 inhibitors, with the most potent one – compound C17 \(IC50 = 0,68 μM\). In the poses obtained in docking, the compound formed molecular interactions with all crucial CBR1 amino acid residues\: Ser139, Tyr 193, Met234 \(H\-bonds\) and Trp229 \(π\-π hydrophobic interaction\). The aim of the second part of the research was to analyse the potential of ASP9521 to inhibit CBR1. The compound is recognised as a potent AKR1C3 inhibitor, with structural features typical for CBR1 inhibitors. Docking studies confirmed that ASP9521 can form the same molec"]

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