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The serotonin 2A(5-HT2A) receptor has been implicated in several neurological conditions and potent 5-HT2A antagonists have therapeutic effects in the treatment of schizo phrenia and depression.In this study,a potent novel 5-HT2A inhibitor 05245768 with a Ki value of (593.89±34.10) nmol/L was discovered by integrating a set of computational approaches and experiments(protein structure prediction,pharmacophore-based virtual screening,automated molecular docking and pharmacological bioassay).The 5-HT2A receptor showed a negatively charged bin-ding pocket.The binding mode of compound 05245768 with 5-HT2A was obtained by GOLD docking procedure,which revealed the conserved interaction between protonated nitrogen in compound 05245768 and carboxylate group of D3.32 at the active site of 5-HT2A.
The serotonin 2A (5-HT2A) receptor has been implicated in several neurological conditions and potent 5-HT2A antagonists have therapeutic effects in the treatment of schizo phrenia and depression. In this study, a potent novel 5-HT2A inhibitor 05245768 with a Ki value of (593.89 ± 34.10) nmol / L was discovered by integrating a set of computational approaches and experiments (protein structure prediction, pharmacophore-based virtual screening, automated molecular docking and pharmacological bioassay). The 5-HT2A receptor showed a negatively charged bin- ding pocket. The binding mode of compound 05245768 with 5-HT2A was obtained by GOLD docking procedure, which revealed the conserved interaction between protonated nitrogen in compound 05245768 and carboxylate group of D3.32 at the active site of 5-HT2A.