Identification of novel serotonin 2C receptor ligands by sequential virtual screening

Bioorg Med Chem. 2009 Jul 1;17(13):4559-68. doi: 10.1016/j.bmc.2009.05.003. Epub 2009 May 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / chemistry*
  • Antidepressive Agents / pharmacology*
  • Appetite Depressants / chemistry*
  • Appetite Depressants / pharmacology*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Drug Design
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Protein Binding
  • Receptor, Serotonin, 5-HT2C / chemistry
  • Receptor, Serotonin, 5-HT2C / metabolism*
  • Serotonin 5-HT2 Receptor Agonists*
  • Structure-Activity Relationship

Substances

  • Antidepressive Agents
  • Appetite Depressants
  • Ligands
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT2 Receptor Agonists