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Information × Registration Number 0222U000427, 0120U105018 , R & D reports Title Study of excitability of primary nociceptive neurons of the peripheral nervous system: the first year of the project popup.stage_title Head Kryshtal Oleh O., Доктор біологічних наук Registration Date 09-01-2022 Organization Bogomolets Institute of Physiology of the National Academy of Sciences of Ukraine popup.description2  At the previous stage of work with 43 synthesized new chemical scaffolds - antagonists of the target receptor, using modern electrophysiological techniques, screening of their activity against potential-directed sodium ion channels in neurons of DCG at a concentration of 100 μm / l. The obtained data allowed to determine the most active and promising compounds. At this stage, the data obtained allowed us to determine that the most active compounds are able to concentration-dependently inhibit the activity of potential-directed sodium ion channels Nav1.7. Testing of the antinociceptive activity of the leader compounds at a concentration of 100 μM / l in the skin-nerve model ex vivo, showed that the compound Z1325487222 slightly inhibits the nociceptive signal from a single isolated sensory nerve ending. Further biological studies are planned to find more active compounds that will inhibit the activity of potential-targeted sodium ion channels Nav1.7 at lower concentrations. The use of an approach that includes complex modeling of regulators taking into account the structure of the potential target and the task of synthesizing simulated compounds, allowed to identify several series of new compounds - inhibitors of TRPV1 and TRPV4 channels (Transient Receptor Potential channels). Several new chemical scaffolds of target receptor antagonists have been proposed, and 68 compounds have been synthesized. The structure of the compounds was confirmed by nuclear magnetic resonance on protons, as well as by chromato-mass spectrometry. A model of the interaction of the ion channel and the microtubule on the membrane surface was created. Using modern electrophysiological techniques, the project screened the activity of synthesized compounds (68 molecules) against TRPV1 and TRPV4 channels in DCG neurons at a concentration of 100 μM / L. The obtained data allowed to identify 23 most active and promising compounds. Product Description popup.authors Maximyuk Olexandr P Romanov Artur K Stefanenko Maria V Fedoryuk Mykhailo P popup.nrat_date 2022-03-09 Close