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Information × Registration Number 0221U106631, 0120U104732 , R & D reports Title Development and in vivo testing of inhibitors of protein kinase C beta, a key enzyme of neutrophilic extracellular traps (NETs) induction, for prevention of acute respiratory distress syndrome (ARDS) popup.stage_title Head Yarmoliuk Serhii M., Доктор хімічних наук Registration Date 16-12-2021 Organization Institute of Molecular Biology and Genetics of NAS of Ukraine popup.description2  Results and novelty – as a result of the work, the optimization of ligand-oriented pharmacophore models of human PKCB protein kinase inhibitors developed at the previous stage was carried out. According to the results of pharmacophore screening, 4,500 compounds were selected. Molecular docking was performed at the ATP-binding site of PKCB and 600 compounds were selected. The results of these screenings were superimposed. In consequence, for in vitro / in vivo testing, 48 preferred compounds were selected from both screenings. The number of extracellular neutrophil traps (NETs) in isolated rabbit neutrophils was also determined. The effectiveness of the protein kinase C beta inhibitors action as a key enzyme of activation of neutrophilic granulocytes with the formation of NETs was determined and the dose-dependence of their activity was evaluated. To estimate inhibitory activity of tested compounds on in vitro protein kinase C beta, enzyme-linked immunosorbent assay (ELISA) was also performed. Thus, promising compounds that can be used as NETose blockers to prevent the development of ARDS have been identified. For best compounds, cytotoxicity was tested on cardiomyocytes system. Also, these compounds have been used for rat experimental ARDS treatment. Product Description popup.authors Bdzhola Volodymyr G. Volynets Halyna Petrivna Kozak Taisiya O. Pashevin Denis О. Polishchuk Valentyna O Protopopov Mykola V. Starosyla Serhiy А. Stroy Dmitro О. popup.nrat_date 2021-12-16 Close