Identification of novel serotonin 2C receptor ligands by sequential virtual screening.
Pharmacophore modelling, docking and virtual screening have become important tool in drug discovery process. Serotonin 2C (5-HT(2C)) receptor ligands have got major attention for their therapeutic uses as antidepressant and anorectic agents. Two step pharmacophore and docking based virtual screening was done using 5-HT(2C) agonists. Two common feature pharmacophore directed virtual hits had submicromolar activity. Refined pharmacophore with excluded volumes was constructed and combined with homology model based docking. Best hit from this virtual screening showed IC(50) of 20.1 nM. Similarity search of this hit compound resulted more active ligand with 7.8 nM activity.
Ahmed
Asif
A
Center for Chemoinformatics Research, Life Sciences Division, Korea Institute of Science and Technology, Cheongryang, Seoul, South Korea.
Choo
Hyunah
H
Cho
Yong Seo
YS
Park
Woo-Kyu
WK
Pae
Ae Nim
AN
D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry* / Q000494:pharmacology*; D001067:Appetite Depressants / Q000737:chemistry* / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D044405:Receptor, Serotonin, 5-HT2C / Q000737:chemistry / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists; D013329:Structure-Activity Relationship
D000928:Antidepressive Agents; D001067:Appetite Depressants; D008024:Ligands; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists