Similarity- and substructure-based development of β2-adrenergic receptor ligands based on unusual scaffolds

Schmidt, Denis and Gunera, Jakub and Baker, Jillian G. and Kolb, Peter (2017) Similarity- and substructure-based development of β2-adrenergic receptor ligands based on unusual scaffolds. ACS Medicinal Chemistry Letters . ISSN 1948-5875

[img] PDF - Repository staff only until 27 March 2018. - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (1MB)
[img] PDF - Repository staff only until 27 March 2018. - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (1MB)

Abstract

The β2-adrenergic receptor (β2AR) is a G protein-coupled receptor (GPCR) and a well-explored target. Here, we report the discovery of 13 ligands, ten of which are novel, of this particular GPCR. They have been identified by similarity- and substructure-based searches using multiple ligands, which were described in an earlier study, as starting points. Of note, two of the molecules used as queries here distinguish themselves from other β2AR antagonists by their unique scaffold. The molecules described in this work allow us to explore the ligand space around the previously reported molecules in greater detail, leading to insights into their structure−activity relationship. We also report experimental binding and selectivity data and putative binding modes for the novel molecules.

Item Type: Article
Keywords: Docking; SAR-by-catalog; Similarity searches; β2-adrenergic receptor
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: 10.1021/acsmedchemlett.6b00363
Depositing User: Eprints, Support
Date Deposited: 24 Apr 2017 08:35
Last Modified: 21 Sep 2017 06:36
URI: http://eprints.nottingham.ac.uk/id/eprint/42190

Actions (Archive Staff Only)

Edit View Edit View