Kim, Hye-Jung Doddareddy, Munikurnar Reddy Choo, Hyunah Cho, Yong Seo No, Kyoung Tai Park, Woo-Kyu Pae, Ae Nim 2024-01-21T00:02:34Z 2024-01-21T00:02:34Z 2021-08-31 2008-01 1549-9596 https://pubs.kist.re.kr/handle/201004/133861 Serotonin 5-HT6 receptor antagonists are thought to play an important role in the treatment of psychiatry, Alzheimer's disease, and probably obesity. To find novel and potent 5-HT6 antagonists and to provide a new idea for drug design, we used a ligand-based pharmacophore to perform the virtual screening of a commercially available database. A three-dimensional common feature pharmacophore model was developed by using the HipHop program provided in Catalyst software and was used as a query for screening the database. A recursive partitioning (RP) model which can separate active and inactive compounds was used as a filtering system. Finally a sequential virtual screening procedure (SQSP) was conducted, wherein both the common feature pharmacophore and the RP model were used in succession to improve the results. Some of the hits were selected based on druglikeness, ADME properties, structural diversity, and synthetic accessibility for real biological evaluation. The best hit compound showed a significant IC50 value of 9.6 nM and can be used as a lead for further drug development. English AMER CHEMICAL SOC SCORING FUNCTION RECEPTORS BINDING RAT 5-HYDROXYTRYPTAMINE-6 ANTAGONISTS EXPRESSION DOPAMINE DYNAMICS AFFINITY New serotonin 5-HT6 ligands from common feature pharmacophore hypotheses Article 10.1021/ci700160t 1 JOURNAL OF CHEMICAL INFORMATION AND MODELING, v.48, no.1, pp.197 - 206 JOURNAL OF CHEMICAL INFORMATION AND MODELING 48 1 197 206 scie scopus 000252713700020 2-s2.0-39449097912 Chemistry, Medicinal Chemistry, Multidisciplinary Computer Science, Information Systems Computer Science, Interdisciplinary Applications Pharmacology & Pharmacy Chemistry Computer Science Article SCORING FUNCTION RECEPTORS BINDING RAT 5-HYDROXYTRYPTAMINE-6 ANTAGONISTS EXPRESSION DOPAMINE DYNAMICS AFFINITY 5-HT6 receptor pharmacophore serotonin