Abnormal deposition or aggregation of protein alpha-synuclein and tau in the brain leads to neurodegenerative disorders. Excessive hyperphosphorylation of tau protein and aggregations destroys the microtubule structure resulting in neurofibrillary tangles in neurons and affecting cytoskeleton structure, mitochondrial axonal transport, and loss of synapses in neuronal cells. Tau tubulin kinase 1 (TTBK1), a specific neuronal kinase is a potential therapeutic target for neurodegenerative disorders as it is involved in hyperphosphorylation and aggregation of tau protein. TTBK inhibitors are now the subject of intense study, but limited numbers are found. Hence, this study involves structure-based virtual screening of TTBK1 inhibitor analogs to obtain efficient compounds targeting the TTBK1 using docking, molecular dynamics simulation and protein-ligand interaction profile. The initial analogs set containing 3884 compounds was subjected to Lipinski rule and the non-violated compounds were selected. Docking analysis was done on 2772 compounds through Autodock vina and Autodock 4.2. Data Warrior and SwissADME was utilized to filter the toxic compounds. The stability and protein-ligand interaction of the docked complex was analyzed through Gromacs and VMD. Molecular simulation results such as RMSD, Rg, and hydrogen bond interaction along with pharmacokinetic properties showed CID70794974 as the potential hit targeting TTBKl prompting the need for further experimental investigation to evaluate their potential therapeutic efficacy in Alzheimer's disease., Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00242-z., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)