3D-Quantitative structure-activity relationship and docking studies of the tachykinin NK3 receptor.

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Geldenhuys WJ, Simmons MA

3D-Quantitative structure-activity relationship and docking studies of the tachykinin NK3 receptor.

Bioorg Med Chem Lett. 2011 Dec 15;21(24):7405-11. doi: 10.1016/j.bmcl.2011.10.014. Epub 2011 Oct 12.

PubMed ID

22056747 [ View in PubMed

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Abstract

The tachykinin NK(3) receptor (NK(3)R) is a novel drug target for schizophrenia and drug abuse. Since few non-peptide antagonists of this G protein-coupled receptor are available, we have initiated this study to gain a better understanding of the structure-activity relationships of NK(3) antagonist compounds. We developed a 3D comparative molecular similarity index analysis (CoMSIA) model that gave cross-validated PLS values with q(2) >0.5 which were validated using a test set. We also describe the development of a homology model of the NK(3)R. The model was then used to develop a pharmacophore for docked ligands. This pharmacophore showed two aromatic, two hydrogen donor and one acceptor/aromatic points. These data will be useful for future structure-based drug discovery of ligands for the NK(3)R.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Talnetant	Neuromedin-K receptor	Ki (nM)	2.51	N/A	N/A	Details