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Notably, there has been no reception of approval for an orally available drug to serve this purpose, to date. In this study, we targeted IL\u20106R\u03b1 to inhibit IL\u20106R\u03b1\/gp130 interaction. The selection of the lead candidate L821 involved the amalgamation of three drug discovery approaches. This library was screened employing tertiary structure\u2010based pharmacophore models followed by molecular docking models, scaffold\u2010hopping, MM\/PBSA as well as MM\/GBSA analysis, and assessments of pK<jats:sub>i<\/jats:sub> and ADMET properties. After evaluating the binding interactions with key amino acids, 15 potential ligands were chosen, with the top ligand undergoing further investigation by means of molecular dynamics simulations. Considering the stability of the complexes, the strong interactions observed between ligand and residues of IL\u20106R\u03b1\/gp130, and the favorable binding free energy calculations, L821 emerged as the prime candidate for inhibiting IL\u20106R\u03b1. Notably, L821 exhibited a docking\u2010based binding affinity of \u22129.5\u2005kcal\/mol. 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