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Information × Registration Number 0224U033030, (0124U003843) , R & D reports Title Cross-talk between GABAARs and ASICs as a novel target for stress-induced insomnia. popup.stage_title Взаємодія між ГАМКА рецепторами та ASIC каналами у якості новітньої молекулярної мішені для терапії стрес-індукованої інсомнії. Підготовчий етап. Head Krishtal Oleg O., Доктор біологічних наук Registration Date 16-12-2024 Organization Bogomolets Institute of Physiology of the National Academy of Sciences of Ukraine popup.description1 The project aims to develop the latest chemical probes using chemical genetics methods to modulate the activity of GABA receptors and ASIC channels and the subsequent application of the obtained data for the correction of sleep disorders. In addition, the project will provide fundamental knowledge about the role of ASIC channels in the regulation of circadian activity. popup.description2 Insomnia is a serious problem that affects about 1/3 of the adult population, and in Ukraine this situation is exacerbated due to the consequences of the war. Using chemoinformatics and computer modeling, small molecular chemical probes were developed, in silico analysis was performed, pharmacophore models were built, and compounds were tested in vitro. The most promising of them will be used for in vivo modeling of stress-induced insomnia. An integrated approach was proposed for the first time, including molecular docking, dynamics, synthesis, screening, and modeling. A library of conformationally constrained GABA analogs on spiro[3.3]heptane and spiro[2.3]hexane scaffolds was created. The synthesized amino acids will be used for biological testing. The obtained compounds have fixed functional group release vectors, which allows us to study the selectivity of ligand-receptor binding. An in silico study of ASIC1a channel blocking was conducted, a new receptor-ligand interaction map and a virtual screening model were created. Critical structural elements for the activity of the compounds were identified. Further, optimization and synthesis of new compounds will be carried out to test their biological activity in accordance with the overall project plan. Product Description popup.authors Yehorova Olena V. Kryshtal Oleh O. Kulyk Viacheslav B. Cherninskyi Andrii О. popup.nrat_date 2024-12-16 Close