Özet:

Computational drug design; has turned into one of the leading fields of medical engineering by speeding up the drug development process and reducing the cost. MS Disease continues to be a major target for drug development studies, as it results in death and reduces the quality of life in patients. Sphingosine-1-phosphate receptor 1 (S1P1) is a G protein-coupled receptor and is active in an important mechanism that leads to the expression and progression of the symptoms of MS. This makes S1P1 an important target for drug development studies. Although preclinical and clinical studies on S1P1 modulation have been identified in the literature, modulators with high selectivity have not been found. Within the scope of our study, pharmacophore modeling was applied via the PharmaGist Web server to S1P1 modulators accessed through the BindingDB database. This method is based on the process of flexible superposition of ligands. Then, molecular docking was performed with the Autodock Vina program, and the results were compared with the S1P1 antagonist in the literature. According to the best pharmacophore models of PharmaGist, 80 molecules were obtained from the ZINCPharmer database, and in silico, ADME/Toxicology was implemented to these molecules. The 4 molecules obtained by ADME/toxicology examination are ZINC00390492, ZINC67740009, ZINC19847253, and ZINC19847241. The binding profiles of all molecules were determined to be similar to the literature and the ML5 antagonist, but the binding affinity (-8.6 kcal/mol) of the ZINC00390492 molecule was found to be less than the binding affinity of the ML5 antagonist (-8.4 kcal/mol). As a result, with this study, it has been demonstrated by computational studies that the ZINC00390492 molecule can be a promising therapeutic agent for the treatment of MS Disease.

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