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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Detalles Bibliográficos
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
Descripción
Sumario:[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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