Insights into the discovery of new 5-HT1A receptor ligands: receptor based pharmacophore

Abstract

Abstract: 5-HT1A receptor is a crucial therapeutic target for the treatment of anxiety, depression, pain, etc. Design and preparation of potent 5-HT1Areceptor ligands for drug discovery has attracted extensive attention in the past few years. In this paper, a three dimensional model of human 5-HT1A receptor was constructed by means of homology modeling. And the docking of MP349 to the receptor suggested a reliable binding mode for 5-HT1A receptor ligand. Based on this ligand-receptor binding mode, an elaborate receptor structure based pharmacophore model was established, which revealed many important features responsible for ligand and 5-HT1A receptor interactions. A virtual screening experiment verified the ability of this pharmacophore model to discover true 5-HT1A receptor ligand. The results of this research would provide important information for further optimizations of 5-HT1A receptor ligands and guide related new lead discoveries.

Key words: 5-HT1A receptor, 5-HT1A receptor, Homology modeling, Homology modeling, Docking, Docking, Pharmacophore, Pharmacophore, Virtual screening, Virtual screening

CLC Number:

R916.1

Supporting:

Zhi-Yu Yang, Wei Lv, Ran Tian, Hong-Wei Jin, Hui-Hui Zeng^*. Insights into the discovery of new 5-HT1A receptor ligands: receptor based pharmacophore[J]. .

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