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

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 we...

Full description

Bibliographic Details
Main Authors: Schmidt, Denis, Gunera, Jakub, Baker, Jillian G., Kolb, Peter
Format: Article
Published: American Chemical Society 2017
Subjects:
Online Access:https://eprints.nottingham.ac.uk/42190/
_version_ 1848796440566956032
author Schmidt, Denis
Gunera, Jakub
Baker, Jillian G.
Kolb, Peter
author_facet Schmidt, Denis
Gunera, Jakub
Baker, Jillian G.
Kolb, Peter
author_sort Schmidt, Denis
building Nottingham Research Data Repository
collection Online Access
description 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.
first_indexed 2025-11-14T19:48:01Z
format Article
id nottingham-42190
institution University of Nottingham Malaysia Campus
institution_category Local University
last_indexed 2025-11-14T19:48:01Z
publishDate 2017
publisher American Chemical Society
recordtype eprints
repository_type Digital Repository
spelling nottingham-421902020-05-04T18:39:15Z https://eprints.nottingham.ac.uk/42190/ Similarity- and substructure-based development of β2-adrenergic receptor ligands based on unusual scaffolds Schmidt, Denis Gunera, Jakub Baker, Jillian G. Kolb, Peter 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. American Chemical Society 2017-03-27 Article PeerReviewed Schmidt, Denis, Gunera, Jakub, 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 Docking; SAR-by-catalog; Similarity searches; β2-adrenergic receptor http://pubs.acs.org/doi/abs/10.1021/acsmedchemlett.6b00363 doi:10.1021/acsmedchemlett.6b00363 doi:10.1021/acsmedchemlett.6b00363
spellingShingle Docking; SAR-by-catalog; Similarity searches; β2-adrenergic receptor
Schmidt, Denis
Gunera, Jakub
Baker, Jillian G.
Kolb, Peter
Similarity- and substructure-based development of β2-adrenergic receptor ligands based on unusual scaffolds
title Similarity- and substructure-based development of β2-adrenergic receptor ligands based on unusual scaffolds
title_full Similarity- and substructure-based development of β2-adrenergic receptor ligands based on unusual scaffolds
title_fullStr Similarity- and substructure-based development of β2-adrenergic receptor ligands based on unusual scaffolds
title_full_unstemmed Similarity- and substructure-based development of β2-adrenergic receptor ligands based on unusual scaffolds
title_short Similarity- and substructure-based development of β2-adrenergic receptor ligands based on unusual scaffolds
title_sort similarity- and substructure-based development of β2-adrenergic receptor ligands based on unusual scaffolds
topic Docking; SAR-by-catalog; Similarity searches; β2-adrenergic receptor
url https://eprints.nottingham.ac.uk/42190/
https://eprints.nottingham.ac.uk/42190/
https://eprints.nottingham.ac.uk/42190/