Identification of Novel Adenosine A(2A) Receptor Antagonists by Virtual Screening

[Image: see text] Virtual screening was performed against experimentally enabled homology models of the adenosine A(2A) receptor, identifying a diverse range of ligand efficient antagonists (hit rate 9%). By use of ligand docking and Biophysical Mapping (BPM), hits 1 and 5 were optimized to potent a...

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Autores principales: Langmead, Christopher J., Andrews, Stephen P., Congreve, Miles, Errey, James C., Hurrell, Edward, Marshall, Fiona H., Mason, Jonathan S., Richardson, Christine M., Robertson, Nathan, Zhukov, Andrei, Weir, Malcolm
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2012
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308209/
https://www.ncbi.nlm.nih.gov/pubmed/22250781
http://dx.doi.org/10.1021/jm201455y
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author Langmead, Christopher J.
Andrews, Stephen P.
Congreve, Miles
Errey, James C.
Hurrell, Edward
Marshall, Fiona H.
Mason, Jonathan S.
Richardson, Christine M.
Robertson, Nathan
Zhukov, Andrei
Weir, Malcolm
author_facet Langmead, Christopher J.
Andrews, Stephen P.
Congreve, Miles
Errey, James C.
Hurrell, Edward
Marshall, Fiona H.
Mason, Jonathan S.
Richardson, Christine M.
Robertson, Nathan
Zhukov, Andrei
Weir, Malcolm
author_sort Langmead, Christopher J.
collection PubMed
description [Image: see text] Virtual screening was performed against experimentally enabled homology models of the adenosine A(2A) receptor, identifying a diverse range of ligand efficient antagonists (hit rate 9%). By use of ligand docking and Biophysical Mapping (BPM), hits 1 and 5 were optimized to potent and selective lead molecules (11–13 from 5, pK(I) = 7.5–8.5, 13- to >100-fold selective versus adenosine A(1); 14–16 from 1, pK(I) = 7.9–9.0, 19- to 59-fold selective).
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spelling pubmed-33082092012-03-20 Identification of Novel Adenosine A(2A) Receptor Antagonists by Virtual Screening Langmead, Christopher J. Andrews, Stephen P. Congreve, Miles Errey, James C. Hurrell, Edward Marshall, Fiona H. Mason, Jonathan S. Richardson, Christine M. Robertson, Nathan Zhukov, Andrei Weir, Malcolm J Med Chem [Image: see text] Virtual screening was performed against experimentally enabled homology models of the adenosine A(2A) receptor, identifying a diverse range of ligand efficient antagonists (hit rate 9%). By use of ligand docking and Biophysical Mapping (BPM), hits 1 and 5 were optimized to potent and selective lead molecules (11–13 from 5, pK(I) = 7.5–8.5, 13- to >100-fold selective versus adenosine A(1); 14–16 from 1, pK(I) = 7.9–9.0, 19- to 59-fold selective). American Chemical Society 2012-01-17 2012-03-08 /pmc/articles/PMC3308209/ /pubmed/22250781 http://dx.doi.org/10.1021/jm201455y Text en Copyright © 2012 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org.
spellingShingle Langmead, Christopher J.
Andrews, Stephen P.
Congreve, Miles
Errey, James C.
Hurrell, Edward
Marshall, Fiona H.
Mason, Jonathan S.
Richardson, Christine M.
Robertson, Nathan
Zhukov, Andrei
Weir, Malcolm
Identification of Novel Adenosine A(2A) Receptor Antagonists by Virtual Screening
title Identification of Novel Adenosine A(2A) Receptor Antagonists by Virtual Screening
title_full Identification of Novel Adenosine A(2A) Receptor Antagonists by Virtual Screening
title_fullStr Identification of Novel Adenosine A(2A) Receptor Antagonists by Virtual Screening
title_full_unstemmed Identification of Novel Adenosine A(2A) Receptor Antagonists by Virtual Screening
title_short Identification of Novel Adenosine A(2A) Receptor Antagonists by Virtual Screening
title_sort identification of novel adenosine a(2a) receptor antagonists by virtual screening
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308209/
https://www.ncbi.nlm.nih.gov/pubmed/22250781
http://dx.doi.org/10.1021/jm201455y
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